The ultrasonographic detection of follicular rupture at the time of intrauterine insemination: is it really decisive?

Our aim is to assess the impact of the ultrasonographic detection of follicular rupture on the intrauterine insemination success. A total of 313 women undergoing ovarian stimulation for intrauterine insemination were enrolled. Transvaginal ultrasonography was performed to check whether the dominant follicle had ruptured and according to that the patients were divided into two groups. The ultrasound detection of follicular rupture was observed in 156 patients (54%). The independent variables favoring follicular rupture were: Age (t: 7.646, p < 0.0005), FSH value (t: -5.637, p < 0.0005), duration of infertility (t: -4.265, p < 0.0005), menstrual cycle length (t: -4.927, p < 0.0005). Moreover, the logistic regression analysis demonstrated that the predictive variables for follicular rupture were: FSH value (OR 1.7, CI 95% 1.3-2.3, p < 0.0005), duration of infertility (OR 2.6, CI 95% 1.6-4.2, p < 0.0005) and menstrual cycle length (OR 2.4, CI 95% 1.7-3.4, p < 0.0005). Pregnancy occurred in 23 patients of the group A (14.7%) and in 22 patients of the group B (16.5%) without a significant difference (p = 0.6). The logistic regression analysis confirmed that neither the evidence of follicular rupture nor any other variables influenced the pregnancy rate.

The role of ovarian fossa evaluation in patients with ovarian endometriosis.

PURPOSE: The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma. METHODS: Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out. RESULTS: 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p < 0.0001). Pain symptoms were more frequent in patients with endometriomas adhesion to the ovarian fossa. CA125 levels were not statistically significantly different between groups. At 12-month follow-up, four patients presented endometrioma recurrence. All of them presented adhesion of the ovarian fossa to the endometrioma in the first operation. CONCLUSIONS: There is a strong association between adhesion of the endometriomas to the ovarian fossa and the presence of endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

Bisphenol A and the female reproductive tract: an overview of recent laboratory evidence and epidemiological studies.

Bisphenol A (BPA) is a high production volume monomer used for making a wide variety of polycarbonate plastics and resins. A large body of evidence links BPA to endocrine disruption in laboratory animals, and a growing number of epidemiological studies support a link with health disorders in humans. The aim of this review is to summarize the recent experimental studies describing the effects and mechanisms of BPA on the female genital tract and to compare them to the current knowledge regarding the impact of BPA impact on female reproductive health. In particular, BPA has been correlated with alterations in hypothalamic-pituitary hormonal production, reduced oocyte quality due to perinatal and adulthood exposure, defective uterine receptivity and the pathogenesis of polycystic ovary syndrome. Researchers have reported conflicting results regarding the effect of BPA on premature puberty and endometriosis development. Experimental studies suggest that BPA's mechanism of action is related to life stage and that its effect on the female reproductive system may involve agonism with estrogen nuclear receptors as well as other mechanisms (steroid biosynthesis inhibition). Notwithstanding uncertainties and knowledge gaps, the available evidence should be seen as a sufficient grounds to take precautionary actions against excess exposure to BPA.

Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping.

Metabolic syndrome is an increasing pathology in adults and in children, due to a parallel rise of obesity. Sedentary lifestyle, food habits, cultural influences and also a genetic predisposition can cause dyslipidemia, hypertension, abdominal obesity and insulin resistance which are the two main features of metabolic syndrome. Polycystic ovary syndrome (PCOS) is a condition directly associated with obesity, insulin resistance (HOMA index) and metabolic syndrome, and it is very interesting for its relationship and overlap with the metabolic syndrome. The relationship between the two syndromes is mutual: PCOS women have a higher prevalence of metabolic syndrome and also women with metabolic syndrome commonly present the reproductive/endocrine trait of PCOS. Prevention and treatment of metabolic syndrome and PCOS are similar for various aspects. It is necessary to treat excess adiposity and insulin resistance, with the overall goals of preventing cardiovascular disease and type 2 diabetes and improving reproductive failure in young women with PCOS. First of all, lifestyle changes, then pharmacological therapy, bariatric surgery and laparoscopic ovarian surgery represent the pillars for PCOS treatment.

Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study.

Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors - Galectin-3 and Stimulation Expressed Gene 2 - in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis.

Doppler velocimetry of the ovarian artery as a tool to detect LH surge in stimulated cycles.

Our aim was to assess the velocimetric pattern of the ovarian artery as a possible marker of LH surge in stimulated cycles. A total of 130 women undergoing ovarian stimulation for intrauterine insemination were randomized in two groups. Each woman was stimulated with 75 IU of recombinant FSH starting from the third day of the cycle. Velocimetric indices of the dominant ovarian artery were compared between patients with spontaneous LH surge and those needing HCG administration to trigger dominant follicle rupture. The pulsatility index and the ratio between peak systolic flow and lowest diastolic flow were significantly higher in women that had a spontaneous triggering of ovulation. These parameters had a high and very significant positive correlation with the dosage of luteinizing hormone. Threshold values of 2.60 for PI and 7.68 for S/D had a high sensitivity and specificity to predict LH surge. These velocimetric results demonstrated that an increased resistance in the dominant ovarian artery is correlated to LH surge in stimulated cycles. It may represent a sign of relevant clinical utility in timing of intrauterine insemination and/or natural intercourse.

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate.

PURPOSE: To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery. METHODS: The inclusion criteria of this study were: (1) 25-40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma. RESULTS: In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01). CONCLUSIONS: Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.

Multiple intraepithelial neoplasias of the lower female genital tract: the reliability of HPV mRNA test.

OBJECTIVE: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms. MATERIALS AND METHODS: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment. RESULTS: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02). CONCLUSIONS: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

Can Doppler study of the ovarian artery predict the fertility outcome of intrauterine insemination?

BACKGROUND: To test the velocimetric pattern of the ovarian artery as a routine ovarian reserve test. METHODS: We enrolled 317 consecutive patients from January 2011 to June 2012. At the second day of the menstrual cycle, a transvaginal ultrasound was performed to evaluate the antral follicle count and ovarian volume, and Doppler of both ovarian arteries was also performed. Controlled ovarian stimulation was performed and the patients were divided in two groups according to the result of the intrauterine insemination: group A (nonpregnant women) and group B (pregnant women). RESULTS: Ovarian velocimetric pattern was similar between the two groups. Follicle stimulating hormone value had a significant correlation with the ultrasound markers; however, the multiple regression linear analysis showed that the only independent variables were the antral follicle count (t = -2.74, p = 0.008) and the systolic/diastolic ratio (t = 3.95, p = 0.0005). The best parameters in predicting the pregnancy were the mean ovarian volume, total and partial antral follicle count between 7 and 10 mm, and the mean resistance index (area under the curve: 0.744, 0.671, 0.667, 0.573, respectively). CONCLUSIONS: The Doppler study of the ovarian arteries did not add significant information about the ovarian reserve status. Only the mean resistance index had a significant diagnostic accuracy, but its specificity (53%) is too low to consider it a screening test.

The influence of endocrine disruptors in a selected population of infertile women.

Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women's reproductive health. We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source. The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects. No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations. Among infertile women, the mean expression of estrogen receptor alpha (ERα) and beta (Erß), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients. The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) did not show significant differences between two groups. Patients with endometriosis had higher levels of PPARγ than all women with other causes of infertility. This study led further support to EDC exposure as a risk factor for women's fertility.

The influence of cigarette smoking on a population of infertile men and women.

PURPOSE: This study aimed at investigating the effect of cigarette smoking on semen parameters in infertile men and on antral follicle count (AFC) and reproductive hormone levels in infertile women. METHODS: In 648 men (200 smokers and 448 non-smokers) sperm concentration, motility and morphology were compared according to smoking status. In the female population, AFC and basal follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured in 296 women (102 smokers and 194 non-smokers). Statistical analysis of data was performed using t test, χ²-test and Spearman's correlation. RESULTS: Among the male population, smokers had significantly lower sperm concentration and motility than non-smokers. Sperm normal morphology was reduced in smokers, although this difference did not reach statistical significance. No significant correlation was found between sperm parameters and the intensity of smoking. In the female population, AFC was reduced in smokers compared with non-smokers. Women who smoked had significantly higher FSH levels. No significant difference was found in LH and estradiol levels according to smoking status. The number of pack-years was negatively correlated to AFC and positively correlated to FSH levels. CONCLUSION: Cigarette smoking is associated with damaging effects on sperm parameters in infertile men and with ovarian reserve alteration in infertile women, as reflected by reduced AFC and increased FSH levels. Every smoker should be encouraged to stop smoking to prevent the damage of the toxins contained in cigarette smoking and preserve their own reproductive potential.

Sonohysterosalpingography: a suitable choice in infertility workup.

PURPOSE: To evaluate the efficacy, compliance, and cost effectiveness of sonohysterosalpingography (HyCoSy) compared with hysteroscopy for uterine cavity evaluation and compared with RX-hysterosalpingography (RX-HSG) for tubal patency determination. METHODS: Three hundred and eight infertile patients underwent HyCoSy, hysteroscopy, and RX-HSG. We compared sensitivity, specificity, positive and negative predictive values (PPV and NPV), discomfort level, and cost of all three procedures. RESULTS: Sensitivity, specificity, PPV, and NPV were higher for HyCoSy than for hysteroscopy but the differences were not significant. HyCoSy also has the same accuracy as RX-HSG. Pain perception and cost were higher for RX-HSG and hysteroscopy than for HyCoSy. CONCLUSIONS: HyCoSy can be regarded as a procedure for initial evaluation of the uterine cavity and of tubal patency in infertile patients.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study.

BACKGROUND: Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. METHODS: One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n=50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. RESULTS: Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. CONCLUSIONS: Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Ovarian stimulation in women with high and normal body mass index: GnRH agonist versus GnRH antagonist.

In modern society, obesity has become a major health problem and has been associated with impaired fertility. The aim of this study is to assess the role of obesity in women undergoing controlled ovarian hyperstimulation (COH) stimulated either with GnRH agonists or with GnRH antagonists. Records of 463 women undergoing in vitro fertilization (IVF) treatment were reviewed. The influence of body mass index (BMI) on treatment outcome was examined, after accounting for differences in stimulation protocols. In the agonist group (286 patients), the total amount of gonadotropins used was significantly higher in patients with a BMI ≥ 25 kg/m², when compared to those with a normal BMI. The same result was found in the antagonist group (177 patients). No significant differences were found in length of stimulation, number of oocytes retrieved or number of embryos transferred. In both the antagonist and the agonist group, the number of clinical pregnancies was found to be higher in patients with normal BMI, suggesting that obesity could impair the ovarian response to exogenous gonadotropins. Considering the results obtained and the many theoretical advantages of GnRH antagonists, ovarian stimulation with GnRH antagonists is an efficient treatment for both women with normal and high BMI.

Laparoscopic injury of the obturator nerve during fertility-sparing procedure for cervical cancer.

BACKGROUND: Intraoperative injury of the obturator nerve has rarely been reported in patients with gynecological malignancies undergoing extensive radical surgeries. Irreversible damage of this nerve causes thigh paresthesia and claudication. Intraoperative repair may be done by end-to-end anastomosis or grafting when achieving tension-free anastomosis is not possible. CASE PRESENTATION: A 28-year-old woman with stage IB cervical cancer underwent fertility-sparing surgery, including conization and bilateral pelvic lymphadenectomy. The left obturator nerve was damaged intraoperatively during pelvic dissection. CONCLUSION: Immediate laparoscopic repair was successful and there was no functional deficit in the left thigh for six months postoperatively.

Life-threatening bleeding after pelvic lymphadenectomy for cervical cancer: endovascular management of ruptured false aneurysm of the external iliac artery.

Late rupture of external iliac artery pseudo-aneurysm is an uncommon complication in patients who undergo extensive gynecologic radical surgeries. A 28-year-old woman with stage IB cervical cancer underwent pelvic lymphadenectomy and extrafascial trachelectomy. Two months after surgery, massive bleeding from ruptured pseudo-aneurysm of the external iliac artery occurred. Endovascular management with covered stent placement was feasible and safe to stop bleeding.

The re-infection rate of high-risk HPV and the recurrence rate of vulvar intraepithelial neoplasia (VIN) usual type after surgical treatment.

BACKGROUND: VIN usual type appears to be related to the HPV's oncogenic types. The aim of this prospective multicenter study was to evaluate the re-infection rate of high-risk HPV and the recurrence rate of VIN usual type after surgical treatment. MATERIAL/METHODS: The study enrolled 103 women affected by VIN usual type. They underwent wide local excision by CO2 laser. The patients were investigated by clinical evaluation and HPV DNA test 6 months after surgical treatment, and then were followed-up at 12, 18, 24, and 36 months. The recurrences were treated with re-excision. RESULTS: The rate of HPV infection after surgical treatment was 34% at 6 months, 36.9% at 12 months, 40% at 18 months, 41.7% at 24 months and 44.7% at 36 months. The mean time from HPV infection to the development of VIN was 18.8 months. CONCLUSIONS: HPV testing in the follow-up of VIN usual type patients might be useful for identifying those patients with a higher risk of recurrence after surgical treatment, although more studies are needed. These preliminary data suggest that the test, in addition to clinical examination, can improve the efficacy of the follow-up.

Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?

Aim of this study was to assess the efficacy of recombinant luteinizing hormone (rLH) supplementation in late follicular phase in multiple follicular stimulation with recombinant follicle stimulating hormone (rFSH) in Triptoreline down-regulated patients undergoing IVF, on preventing clinical OHSS and cycles cancellation for OHSS risk. Nine hundred ninety-nine patients aged ≤ 40 with basal FSH ≤ 12 mUI/Ml were down-regulated before starting rFSH stimulation for oocytes recovery. Patients were allocated in two groups: (A) (501 patients) treated with 150 IU of rFSH eventually adjusting rFSH dosage day 7 of stimulation until recombinant human chorionic gonadotropin (rhCG) administration, (B) (498 patients) treated with 150 IU of rFSH and 75 IU of rLH since day 7 of stimulation until rhCG administration and adjusting rFSH at the same day. E2 the day of rhCG was higher in group B (p < 0.0001); number of cycles cancelled in group A (42/8.3%) for risk of ovarian hyperstimulation syndrome (OHSS) was higher than group B (12/2.4%) (p < 0.000001). We observed an increase in pregnancies in group B compared with group A (16.8% vs 11.9%) (p < 0.05) and we observed also a larger number of clinical OHSS in group A than in group B (p < 0.05).

Vaginal treatment of endometrial cancer: role in the elderly.

BACKGROUND: To compare abdominal hysterectomy, the most currently used for treating cancer of the endometrium, to the vaginal hysterectomy in term of survival, morbidity and failure rates. METHODS: We retrospectively analyzed 68 cases divided into two sub-groups. A study group of 31 cases received vaginal surgery; a control group of 37 cases was treated with a laparotomy. Mean operative time, median hospital stay, intra- and post-operative complications, DFS and OS time as well as occurrence of local or distant recurrences have been evaluated and reported. Cases included patients with a higher rate of medical morbidities (p = 0.01) than controls. RESULTS: Mean age was 76.2 and 70.4 years in the vaginal (V) group and abdominal (A) group respectively. Mean operative time was longer for the group A. Group V patients had a lower mean post-operative hospital stay (p < 0.05). Differences in the two groups regarding intra- and post-operative complications, occurrence of local or distant recurrences and DFS time were not statistically significant. Disease specific survival time at 5 years scored 97% for group V, and 97% for group A. CONCLUSIONS: Results show how vaginal approach had a similar outcome in selected patients. Vaginal surgery could therefore be the proper choice in patients with early stages and lower surgical risk, in addition to elderly patients exposed to a higher surgical risk.

Effect of corticosteroids and progesterone on adrenomedullin output and expression in human fetal membranes and placenta trophoblasts.

OBJECTIVE: Plasma adrenomedullin (AM) concentrations are increased in fetal and maternal circulation in response to exogenous glucocorticoids administration. The role of corticosteroids and progesterone in regulating AM synthesis and secretion was investigated in amnion and chorion trophoblast cells of the fetal membranes and in placental trophoblast cells. STUDY DESIGN: Cells were treated with betamethasone, hydrocortisone, and progesterone. Changes in AM output were measured with radioimmunoassay. Protein expression was evaluated with Western blot and immunohistochemistry. RESULTS: Betamethasone stimulated AM secretion and protein expression in placental trophoblast cells and in amnion cells of the fetal membranes. Hydrocortisone and progesterone did not induce any effect either on secretion or protein expression in placenta and fetal membranes cells. CONCLUSION: Glucocorticoids regulate AM secretion and expression by human placenta thereby promoting increased AM concentration in maternal and fetal circulation in circumstances characterized by increased cortisol levels.