Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women.

PURPOSE: Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach. METHODS: This was a prospective, randomized, parallel group, open label, controlled versus no treatment clinical study. PCOS women aged > 18, free from systemic diseases and from pharmacological treatments were randomized with a 2:1 ratio for treatment with activated micronutrients in support to the carbon cycle (Impryl, Parthenogen, Switzerland-n = 22) or no treatment (n = 10) and followed-up for 3 months. Fasting blood homocysteine, AMH, testosterone, SHBGs, and the resulting FTI were tested before and at the end of the follow-up. RESULTS: The mean baseline fasting blood homocysteine was above the normal limit of 12 µMol/L and inversely correlated with SHBG. AMH was also increased, whereas testosterone, SHBG, and FTI were within the normal limit. The treatment achieved a significant reduction of homocysteine, that did not change in the control group, independently of the starting value. The treatment also caused an increase of AMH and a decrease of SHBGs only in the subgroup with a normal homocysteine at baseline. CONCLUSIONS: In PCOS ladies, blood homocysteine is increased and inversely correlated with the SHBGs. Physiologic amounts of activated micronutrients in support to the carbon cycle achieve a reduction virtually in all exposed patients. Whether this is of clinical benefit remains to be established.

Early ultrasonographic diagnosis of placental mesenchymal dysplasia.

Placental mesenchymal dysplasia (PMD) is a rare pathology characterized by vascular anomalies, placentomegaly and grapelike vesicles resembling partial molar pregnancy. PMD is often associated with fetal growth restriction or intrauterine fetal demise. We report a case of an early diagnosis of PMD at 10 weeks' gestation, with a regular intrauterine growth and a fetal demise occurring at 31 week's gestation. The placenta showed aneurysmally dilated and tortuous vessels with luminal thrombosis. Even in presence of a regular fetal growth, a fetal demise may always occur, suggesting the option of an early heparin administration to reduce the risk of thrombosis of chorionic vessels.

Endometrial carcinoma in women 40 year old or younger: a case report and literature review.

Endometrial cancer is the most frequent gynecologic cancer. Although it mainly occurs in menopausal women, it can hit younger patients as well. Only few cases of affected women under the age of 30 are reported. A case of a 23-year-old patient with endometrioid carcinoma grade II-III is presented. Hysterectomy is considered the standard treatment and it could represent a problem for those young women who desire to preserve fertility. A conservative management can be offered to these patients when the tumor is well differentiated and advanced stage is excluded. Several studies are available in literature about fertility sparing approach. Progestin treatment, combined or not with hysteroscopic ablation seem to be the most validated conservative management. Anyhow this treatment is not free risk, because it is not always effective and disease progression during or after treatment is possible. Then a strict evaluation and selection of patients before starting treatment is mandatory.

Prophylactic arterial catheterization in the management of high risk patients for obstetric haemorrhage.

OBJECTIVES: Post-partum haemorrhage still remains one of the major causes of maternal morbidity and mortality. In case of abnormal placentation it is possible to carry out preventive and therapeutic actions. To maintain fertility in reproductive-aged women and to avoid a more radical surgery, embolization has been introduced in patients at high risk for haemorrhage. To describe a new option in the management of patients with abnormal placentation by an elective, preventive arterial catheterization and selective embolization of pelvic arteries. PATIENTS AND METHODS: A retrospective study including thirty six patients with abnormal placental invasion. All patients were prepared in the angiographic room and preventive arterial catheterization was performed before elective caesarean delivery. Materials for interventional angiography were transferred to the operating room. During surgery, selective embolization of pelvic arteries was realized in case of uncontrolled bleeding. RESULTS: Thirty-six elective arterial catheterizations were performed: 4 cases (11.1%) required embolization, haemorrhage was stopped in 2 patients. Hysterectomy was performed in two cases (5.5%). No death was reported. Two humeral thrombosis (5.5%) were registered. CONCLUSIONS: Prophylactic arterial catheterization appears to be safe. The main advantage is the reduction of the interval between the onset of bleeding and the embolization. This new option of management may contribute to reduce the risk of hysterectomy and maternal death.

Antisepsis regimen in the surgical treatment of HPV generated cervical lesions: polyhexamethylene biguanide vs chlorhexidine. A randomized, double blind study.

INTRODUCTION: To reduce the risk of local infections after surgical treatments for HPV infected cervical lesions, the post-operative regimen is generally based on the use of vaginal antimicrobial agents. AIM: The efficacy and safety of polyhexamethylene biguanide-based vaginal suppositories was compared to a similar chlorhexidine-based treatment, in the post recovery regimen after surgical treatment of cervical lesions. MATERIALS AND METHODS: 50 women who underwent to CO2 laser therapy for cervical lesions were randomly assigned to receive 10 days of antiseptic treatment with chlorhexidine digluconate vaginal suppositories, or polyhexamethylene biguanide vaginal suppositories (Monogin®/Biguanelle® ovuli, Lo.Li. Pharma, Italy). A weekly follow-up check was performed for 6 weeks. RESULTS: Polyhexamethylene biguanide-based treatment showed improved efficacy compared to chlorhexidine, in terms of healing process and prevention of bacterial infections. CONCLUSIONS: Due to its safety and effectiveness, the vaginal treatment with polyhexamethylene biguanide is preferred to chlorexidine, in accordance with previously reported in vitro evidences.

Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS.

Oligomenorrhea and polycystic ovaries in women are one of the most important causes of the high incidence of ovulation failure. This is linked, perhaps, to insulin resistance and related metabolic features. A small number of reports show that myo-inositol improves ovarian function, but in these trials the quality of evidence supporting ovulation is suboptimal. Furthermore, few of them have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 92 patients randomized, 47 received 400 mcg folic acid as placebo, and 45 received myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). The ovulation frequency assessed by the ratio of luteal phase weeks to observa-tion weeks was significantly (P < 0.01) higher in the treated group (25%) compared with the placebo (15%), and the time to first ovulation was significantly (P < 0.05) shorter [24.5 d; 95% confidence interval (CI), 18, 31; compared with 40.5 d; 95% CI, 27, 54]. The number of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of myo-inositol on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the myo-inositol group. A significant increase in circulating high-density lipoprotein was observed only in the myo-inositol-treated group. Metabolic risk factor benefits of myo-inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). After 14-wk myo-inositol or placebo therapy, no change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded. There was an inverse relationship between body mass and treatment efficacy. In fact a significant weight loss (and leptin reduction) (P < 0.01) was recorded in the myo-inositol group, whereas the placebo group actually increased weight (P < 0.05). These data support a beneficial effect of myo-inositol in women with oligomenorrhea and polycystic ovaries in improving ovarian function.

[Treatment of uterine fibromyoma with bilateral uterine artery embolization: state of the art]. / Trattamento di fibromioma dell'utero mediante embolizzazione bilaterale dell'arteria uterina. Stato dell'arte.

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is a minimally invasive alternative procedure in appropriate candidates to conventional myomectomy and hysterectomy for symptomatic uterine leiomyoma, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. In order to completely block the arterial blood supply to the fibroid, UAE is typically performed in both uterine arteries. At 1 year follow-up, the uterus may shrink by up to 55%, however, a re-growth of the fibroid may occur. The rate of major complications and amenorrhea following this procedure is low, ranging in most series from 1% to 3.5% and 1% to 7%, respectively. Nevertheless, the rate of amenorrhea in women over 45 seems to be higher. Women who wish to become pregnant should be cautioned about potential complications during pregnancy. Despite the lack of controlled studies that compared UAE with conventional surgery, and despite limited extended outcome data, UAE has gained rapid acceptance, primarily because this procedure preserves the uterus, is less invasive, and has less short-term morbidity than most surgical options. This review focuses on recent publications evaluating UAE and concludes that it is a safe treatment option, providing substantial improvement in both health-related quality of life and symptom control for most patients, with a very low rate of major complications. Any centre that offers UAE should adhere to published clinical guidelines, maintain ongoing assessment of quality improvement measures, and observe strict criteria to obtain procedural privileges. The gynecologist is likely to be the primary initial consultant to patients who present with myomas symptoms. Therefore, they must be familiar with the indications, exclusions, outcome expectations, and complications of UAE. When hysterectomy is the only option, UAE should be seriously taken into consideration. At this particular moment in time, data are needed from randomized controlled trials comparing UAE with surgical procedures. Current efforts to provide prospective objective assessment of treatment outcomes and complications after UAE will help to optimize women options and clinical guidelines.

The changing role of progesterone in preterm labour.

Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. Although the pharmacokinetics and pharmacodynamics of progesterone have been well studied, and since 1935 it has been synthesised and is now available commercially, its use in the pathophysiology of pregnancy remains controversial. One of these concerns is the way in which the hormone is administered, with parenteral use proving the best way to obtain optimal plasma levels. Another concern is the paucity of randomised controlled trials and the different dosages and populations studied. As a result, the therapeutic application of progesterone in pregnancy is restricted to the prevention and treatment of threatened miscarriage, recurrent miscarriage and preterm birth. Progesterone is efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high risk pregnant women using high-dosage prophylactic progesterone.

Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial.

BACKGROUND: Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A small number of reports shows that inositol improves ovarian function. Futhermore, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of this study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. METHODS: Of the 283 patients randomized, 2 withdrew before treatment commenced, 147 received placebo, and 136 received inositol (100 mg, twice a day). The women which discontined the study prematurely were more numerous in the treatment group (n = 45) than the placebo group (n = 15; P < 0.05). RESULTS: The ovulation frequency estimated by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%). The time in which the first ovulation occurred was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The number of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and in most cases ovulations were characterized by normal progesterone concentrations in both groups. The effect of inositol on follicular maturation was rapid, because the circulating concentration of E2 increased only in the inositol group during the first week of treatment. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the inositol group, whereas in the placebo group was recorded an increase of the weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the inositol-treated group. Metabolic risk factor benefits of inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge test was recorded after 14-wk of inositol and placebo therapy. There was an inverse relationship between body mass of the patients and the efficacy of the treatment. CONCLUSIONS: These data support a beneficial effect of inositol in improving ovarian function in women with oligomenorrhea and polycystic ovaries.

A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide. A prospective, randomized study.

BACKGROUND: Bacterial vaginosis (BV) is the most common vulvovaginal infection and represents the 35% of all the infections occurring in women in the reproductive age. It is well recognised that serious forms of BV can induce several complications among women undergoing gynaecologic or obstetric surgery, having pelvic inflammatory diseases, temporary or absolute infertility, miscarriage and abortion. At present, the clinical treatment of choice of BV is the use of systemic or local (gel or cream) metronidazole and clindamycin, though systemic use has some limitations due to side-effects and contraindications. Polyhexamethylene biguanide (PHMB) is a new bi-biguanide compound having a broad spectrum activity and low toxicity, that have been successfully utilized in ophthalmology and dentistry. Aim of this study was to evaluate the efficacy and tolerability of a single-dose vaginal administration of a PHMB vaginal gel in the treatment of BV in comparison to clindamycin vaginal cream. METHODS: One-hundred and ten patients affected by BV were treated with PHMB vaginal gel in single administration or clindamycin vaginal cream 1 daily administration for 7 days. RESULTS: We demonstrated the therapeutic efficacy of mono-dose administration of a vaginal solution containing PHMB in BV treatment; this efficacy is similar to the one shown in antibiotic therapy. Furthermore, this product was well tolerated by all treated patients. CONCLUSIONS: Mono-dose PHMB treatment should be regarded as the therapy of choice for BV, using clindamycin and metronidazole only for relapses treatment.

A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To compare the effectiveness of i.m. P and 17alpha-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles. DESIGN: Prospective, randomized study. SETTING: Patients undergoing IVF-ET in our Centers. PATIENT(S): The inclusion criteria were the use of GnRH down-regulation and aged <40 years. INTERVENTION(S): A total of 300 cycles were randomly treated with either 17-HPC (341 mg every 3 days) or P (50 mg daily). MAIN OUTCOME MEASURE(S): The outcomes of IVF in both study groups were evaluated for biochemical pregnancy, miscarriage, clinical pregnancy, and ongoing pregnancy. RESULT(S): No difference was found in the main outcome parameters considered. CONCLUSION(S): Although the results of the study encourage the use of 17-HPC for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that it can replace i.m. P-in-oil.

Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes.

OBJECTIVE: To analyze the chromosomal status of human embryos obtained from frozen-thawed oocytes. DESIGN: Fluorescence in situ hybridization analysis of embryos obtained after oocyte cryopreservation. SETTING: Department of Obstetrics and Gynecology at the University of Perugia, Italy, and the Instituto Valenciano de Infertilidad, Spain. PATIENT(S): Oocyte donors (n = 43). Fertilization, development, and chromosomal status of the embryos were compared with a control group (n = 18) of patients undergoing preimplantation genetic diagnosis for sex chromosome-linked diseases. INTERVENTION(S): Collection of oocytes after conventional ovarian stimulation and cryopreservation using propanediol as the cryoprotectant and a slow freezing procedure. Microinjection of surviving metaphase II oocytes and evaluation of fertilization and embryo development up to blastocyst stage. Chromosomal analysis after embryo biopsy. MAIN OUTCOME MEASURE(S): Survival, fertilization, and blastocyst rates. Embryo chromosomal analysis employing specific probes for chromosomes 13,18,21, X and Y. RESULT(S): The overall survival rate was 59.4%. There was no difference between cryopreservation and control groups in fertilization rates (76.5% vs. 90.5%) or blastocyst development (29.6% vs. 35%). The percentage of blastocysts from the original number of cryopreserved oocytes was only 5.6%, comparable to the 5.9% obtained in the control group. The percentage of embryos with abnormal number of chromosomes in the cryopreservation group (28.6%) was comparable to the 26% observed in the controls. CONCLUSION(S): Fertilization and cleavage rates after oocyte freezing are acceptable. Survival is, however, still poor, leading to overall results that make the technique clinically inefficient. There is no increase in the rate of chromosomal abnormalities, indicating that the technique is, nevertheless, safe enough to be further explored and improved.

Low dose of ethinyl estradiol can reverse the antiestrogenic effects of clomiphene citrate on endometrium.

Fifty healthy, voluntary patients aged between 20 and 30 years with regular menstruation and plasmatic progesterone level >10 ng/ml at the midluteal phase have been enrolled in this study. They were randomly treated with clomiphene citrate (CC; group A) or CC + ethinyl estradiol (0.05 mg group B, or 0.02 mg group C). We estimated the difference in uterine artery pulsatily index, endometrial thickness and histological dating and morphometric analysis of endometrium. No significant differences in Pulsatility Index values and in the number of preovulatory follicles were noted. The difference between endometrial thickness, histological dating and morphometric analysis of the endometrium were statistically different between groups B and C vs. A. Our study shows that CC has a deleterious effect on endometrium maturity and that adding ethinyl-E(2) produces a favorable endometrial response even with very low doses.

Use of intramuscular progesterone versus intravenous albumin for the prevention of ovarian hyperstimulation syndrome.

This study was designed to compare the effectiveness of intramuscular progesterone with that of intravenous albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). Ninety-six patients at high risk to develop OHSS (estradiol concentration >9, 000 pmol/l on the day of hCG administration and over 20 follicles of a diameter larger than 14 mm observed by transvaginal ultrasonography) and undergoing in vitro fertilization-embryo transfer were enrolled. They were randomly treated with intramuscular progesterone (200 mg/day) or 100 ml of 20% intravenous albumin in order to estimate the difference in the incidence of OHSS. A significant difference in the incidence of moderate OHSS and no cases of severe OHSS were observed between the groups. Our data show the effectiveness in preventing OHSS with high doses of progesterone.

Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study.

OBJECTIVE: To compare the effectiveness of clomiphene citrate used alone and in combination with ethinyl E2 for the induction of ovulation in patients undergoing IUI. DESIGN: Randomized, double-blind study. SETTING: Four infertility treatment centers. PATIENT(S): Women aged 25-35 years with infertility of at least 2 years' duration and oligomenorrhea or amenorrhea associated with a positive menstrual response to an IM progesterone challenge. INTERVENTION(S): A total of 64 patients were randomized to treatment with CC (100 mg daily for 5 days) or CC (100 mg daily for 5 days) plus ethinyl E2 (0.05 mg daily for 5 days). MAIN OUTCOME MEASURE(S): The uterine artery pulsatility index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. RESULT(S): Both treatment regimens increased FSH, LH, and 17beta-E2 levels, with no statistically significant differences. There was a statistically significant difference in endometrial thickness between the two treatment groups. No statistically significant differences were noted in pulsatility index values or in the number of preovulatory follicles. CONCLUSION(S): Ethinyl E2 can reverse the deleterious effects of CC on endometrial thickness, which may contribute to higher pregnancy rates.

Atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and histology.

OBJECTIVE: A new terminology for cytologic diagnosis of cervical lesions has been introduced by Bethesda System. This includes: 1) Atypical squamous cells of undetermined significance (ASCUS), 2) Low-grade squamous intraepithelial lesion (LSIL), 3) High-grade squamous intraepithelial lesion (HSIL), 4) squamo-cellular carcinoma. The aim of this study was to assess the correlation between the colpocytologic test (Pap psmear), the histologic response and colposcopy. METHODS: We re-examined the cytologic results of 447 patients who underwent routine cytologic tests, with a diagnosis of various grades of atypia, from ASCUS to HSIL. A histologic test was carried out on a colposcopic basis in 210 cases and cytologic results were correlated with the histologic and colposcopic pictures. RESULTS: For ASCUS the histology was positive in 19.1% (31/163) of cases and negative in 10.4% of the colposcopically positive cases (17/163), while in the remaining 70.5% (115/163) the colposcopy resulted negative. In LSIL with the presence of human papillomavirus (HPV) the histologic findings, confirmed the cytologic result in 35.8% (48/134) while in the group of cervical intraepithelial neoplasia (CIN I) results corresponded in 40.6% (41/101). In high squamous intraepithelial lesions there was an histologic confirmation in 59.2% (29/49). CONCLUSIONS: The data obtained indicate an increase in positive histology results from the types of low grade (ASCUS-LSIL) to those of a high grade (HSIL). Our results indicate that the presence of ASCUS should be assessed colposcopically and histologically, where indicated.

Programmed oocyte retrieval.

Several methods of facilitating the work schedule for in vitro fertilization programs have been proposed. LH-RH agonists offer the possibility of manipulating the day of hCG injection and consequently the day of ovum pick-up. Moreover, after desensitization, follicles are contemporarily stimulated and a higher number of mature oocytes are retrieved. The same objective of follicle synchronization can be obtained with progestins, which have the advantage of minor cost and less adverse effects. The use of oral contraceptives offers similar results to those obtained with progestins. The best choice in work programming appears to be a "monitorized programmed oocyte retrieval" with the use of progestins and LH-RH agonists.