Ongoing pregnancy after intracytoplasmic sperm injection of epididymal spermatozoa into cryopreserved human oocytes.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C Flamigni
Publications and source records attributed to C Flamigni.
A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of hirsutism.
Sixty-six hirsute women were randomized and treated with 1) flutamide (n = 15), 250 mg/day; 2) finasteride (n = 15), 5 mg/day; 3) ketoconazole (n = 16), 300 mg/day; and 4) ethinyl estradiol (EE)-cyproterone acetate (CPA; n = 20), 0.01 mg EE/day for the first week, 0.02 mg EE/day for the second week, and 0.01 mg EE/day for the third week, followed by a pause of 7 days, then 12.5 mg CPA/day added during the first 10 days of every month for 12 months. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor in basal conditions and after 90, 180, 270, and 360 days of treatment. All treatments produced a significant decrease in the hirsutism score, hair diameter, and daily hair growth rate: flutamide, -55 +/- 13%, -21 +/- 14%, and -37 +/- 18%; finasteride, -44 +/- 13%, -16 +/- 12%, and -27 +/- 14%; ketoconazole, -53 +/- 18%, -14 +/- 12%, and -30 +/- 21%; and EE-CPA, -60 +/- 18%, -20 +/- 11%, and -28 +/- 21%. Some differences existed among treatments with regard to effectiveness; EE-CPA and flutamide seem to be the most efficacious in improving hirsutism. For the hirsutism score, a greater decrease was seen with EE-CPA (-60 +/- 18%) than with finasteride (-44 +/- 13%; P < 0.01) and a greater decrease was seen with flutamide (-58 +/- 18%) than with finasteride (-44 +/- 13%; P < 0.05). Flutamide is the fastest in decreasing hair diameter; EE-CPA is the fastest in slowing down hair growth, even though at the end of the treatment there was a significant difference between flutamide and finasteride only (-41 +/- 18% vs. -27 +/- 14%; P < 0.05). Flutamide, ketoconazole, and EE-CPA induced a significant decrease in total and free testosterone, 5alpha-dihydrotestosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione plasma levels. During the EE-CPA treatment, gonadotropins were suppressed, and the sex hormone-binding globulin level increased. Finasteride induced a decrease in dehydroepiandrosterone sulfate and 5alpha-dihydrotestosterone and an increase in testosterone levels. Very few side-effects were observed during treatment with low doses of flutamide, EE-CPA, and particularly finasteride. Flutamide induced a decrease whereas EE-CPA induced an increase in triglycerides and cholesterol, showing higher values within the normal range. Ketoconazole induced several side-effects and complications, and several people dropped out of the study. Despite different modalities of action and significantly different effects on androgen levels, low doses of flutamide, finasteride, and EE-CPA constitute very satisfactory alternative therapeutic regimens in the treatment of hirsutism.
Adult↗
A histological and immunohistochemical study of neuropeptide containing somatic nerves in the levator ani muscle of women with genitourinary prolapse.
BACKGROUND: To evaluate the changes occurring in the somatic innervation throughout the levator ani muscle in women with genitourinary prolapse and stress urinary incontinence (SUI). METHODS: Thirty-four patients with genital prolapse entered the study and ten subjects with non-malignant pathologies acted as a control group. All patients were evaluated by urodynamic investigation and an electromyographic study of pelvic floor muscles to define the type of urinary incontinence. Biopsy samples were obtained from both groups of patients: the site of muscle biopsies were left and right part of perirectal pubococcygeus muscle. The evaluation of immunoreactivity was semiquantitative and based on staining intensity and distribution. RESULTS: In all cases, S-100 protein and NSE immunoreactivities were found in nerve fascicles running throughout the striated muscle. NPY and VIP positivities were more intense and diffuse, whereas SP immunoreactivity was quite scanty. The different patterns of NPY and VIP expression changed in relation to degree of genital prolapse and to the presence of SUI. CONCLUSIONS: Our immunohistochemical study shows the presence in the pelvic floor of neurons that are able to synthesize neuropeptides. The lower immunoreactivity score of same neuropeptides (VIP, NPY) observed among patients with third degree genital prolapse and with SUI could be related to biochemical damage of the neurons with subsequent lower production of chemical messengers.
Aged↗
Follicular fluid and human granulosa cell cultures: influence on sperm kinetic parameters, hyperactivation, and acrosome reaction.
OBJECTIVE: To evaluate the influence of human granulosa cell (GC) cultures and follicular fluid (FF) on sperm kinetic parameters, hyperactivation, and the acrosome reaction compared with the influence of human tubal fluid (HTF) and Ham's F-10 medium. DESIGN: Sperm kinetic parameters, hyperactivation, and the acrosome reaction were evaluated after 6 hours of incubation in HTF, Ham's F-10 medium, FF, and GC cultures. SETTING: Infertility and In Vitro Fertilization Centre, Reproductive Endocrinology Unit, Institute of Obstetrics and Gynaecology. PATIENT(S): Sixteen normal semen samples. INTERVENTION(S): Sperm kinetic parameters and hyperactivation were analyzed using an automated videomicrography system, the acrosome reaction was performed using a triple-stain technique, and progesterone and 17OH-progesterone levels were measured with the use of commercially available kits. MAIN OUTCOME MEASURE(S): Sperm kinetic parameters, hyperactivation, acrosome reaction. RESULT(S): The percentage of motile sperm, the mean curvilinear velocity, and the mean of the maximum amplitude of lateral head movement were increased significantly after 6 hours of incubation in FF or GC cultures compared with incubation in HTF or Ham's F-10 medium, whereas the mean linearity was decreased significantly. Follicular fluid and GC cultures significantly increased hyperactivation and the acrosome reaction compared with the values obtained using HTF and Ham's F-10 medium. Progesterone and 17OH-progesterone levels were increased significantly after incubation in FF and GC cultures compared with HTF and Ham's F-10 medium. CONCLUSION(S): Follicular fluid and GC cultures increase sperm motility parameters, hyperactivation, and the acrosome reaction. This effect may be related to GC detoxification of the microenvironement or GC secretion of peptides, glycoproteins, growth factors (insulin-like growth factors 1 and 2), or steroids (progesterone and 17OH-progesterone).
17-alpha-Hydroxyprogesterone↗
Paracrine regulation of menstruation.
Endometrial proliferation, secretion, vascular neoformation and modification to shedding is under direct and/or indirect control of steroid hormones. The progressive modification of the endometrial architecture is due to its growth and differentiation. The new tissue regenerates monthly from a 2-5 mm to a 12-18 mm of complex tissue until it sheds under a co-ordinated network of bioactive molecules produced and activated during the menstrual cycle. The steroid hormones, the HLA-DR and integrin molecules, the intense production of several proteins, the vascular damage, and the disconnection of cell-cell and cell-matrix interaction are participating in both the endometrial preparation for embryonic implantation and the shedding and bleeding of the tissue itself. Menstruation is a process associated with damage to the epithelium, endothelium and extracellular matrix, ending on controlled bleeding, tissue dissolution and repair. Endometrial proteinases and tissue factor (TF) contribute to systemic factors to control the mechanisms of regulation of tissue dissolution, tissue shedding, and vascular bleeding during menstruation.
Animals↗
Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men.
This study was undertaken with the aim of investigating the cytogenetic constitution of normal as well as abnormal spermatozoa and immature germ cells found in semen of normal men and infertile patients. A specific protocol of double in-situ hybridization for chromosomes 1 and 17 based on colorimetric detection of the hybridization signals (ISH) and brightfield microscopy analysis of cellular morphology was applied. Also the influence of paternal age on sperm aneuploidy was investigated. We found that, at least in the age range analysed (28-54 years) and for semen of good quality (total normal motile counts above 10 x 10(6)) (n = 17), paternal age has no influence on baseline rates of sperm aneuploidy. However, with decreasing semen quality (total normal motile sperm counts below 5 x 10(6)) (n = 6) significantly higher rates of sperm aneuploidy for autosomes 1 and 17 were scored (0.8 versus 1.43%) (P < 0.001). Regardless of the type of semen analysed, a number of morphologically abnormal spermatozoa were found to be hyperhaploid or diploid in a high percentage of cases (20 and 10% respectively). The same was found for immature germ cells (aneuploidy rate of 18%). We conclude that in infertile men with poor quality semen a direct relationship may exist between the impairment of the spermatogenesis process (as reflected by an increased production of morphologically and cytogenetically abnormal germ cells) and rates of baseline aneuploidy occurring in normal spermatozoa. Infertile couples undergoing assisted reproduction treatment need to be counselled about the risk of using spermatozoa which may carry higher rates of non-disjunction for different chromosomes. While sperm hyper- or hypohaploidy for some chromosomes (X,Y) implies counselling couples about the risk of abnormal phenotype in their offspring, most autosomal sperm aneuploidies probably translate only into lower rates of embryo fertilization and survival.
Adult↗
Low dose of cyproterone acetate and testosterone enanthate for contraception in men.
After a control phase, 10 normal men received cyproterone acetate (CPA) at a dose of 25 mg/day (CPA-25; n=5) or 12.5 mg/day (CPA-12.5; n=5) plus testosterone enanthate (TE) 100 mg/week, for 16 weeks. Throughout the study sperm counts were performed every 2 weeks, and luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, biochemical and haematological tests were performed every 4 weeks. All five men in group CPA-25 and three men in group CPA-12.5 achieved azoospermia. One man in group CPA-25 was azoospermic by week 12 of hormone administration, but had a sperm count of 0.1 x 10(6)/ml at week 16. Time to azoospermia was 9.0+/-1.3 and 8.7+/-0.7 weeks in groups CPA-25 and CPA-12.5 respectively. Gonadotrophins were decreased by week 4 of hormone administration, remained around the minimum detectability of the assay for the duration of hormone administration and returned to baseline after stopping hormone administration. Testosterone values did not change. No change in any biochemical parameters was found. Haematological parameters were decreased at week 16 of hormone administration and returned to baseline after stopping hormone administration. In conclusion, these results suggest that an hormonal regimen consisting of testosterone plus a progestin with anti-androgenic properties holds promise as an effective, safe and reversible male contraceptive.
Adult↗
Oocyte cryopreservation.
Cryopreservation of human oocytes has been employed with little success in clinical practice, even though it may solve the legal and ethical problems linked to embryo freezing. Various attempts to cryopreserve human oocytes have mostly been unsuccessful, leading to low oocyte survival rates after thawing, and the search for an optimal protocol for oocyte cryopreservation remains elusive. A preliminary study was undertaken to evaluate some of the factors influencing the survival rate of human oocytes and the efficiency of intracytoplasmic sperm injection (ICSI) as an insemination procedure. A total of 38 women with tubal infertility were enrolled in the study. The cryopreservation procedure consisted of a slow freeze-rapid thawing technique using 1,2 propanediol and sucrose as cryoprotectants. The overall oocyte survival rate was approximately 60%. A better survival rate was obtained when the oocytes were cryopreserved in the presence of partially removed cumulus oophorus rather than in the presence of totally enzymatically removed cumulus oophorus. The cryoprotectant concentration and the equilibration time also appear to influence the oocyte survival rate. ICSI may be an efficient method of achieving a satisfactory outcome in terms of fertilization in cryopreserved human oocytes. Embryonic morphological quality does not seem to be compromised by cryopreservation. In conclusion, these data show that cryopreservation may ensure that the integrity of the human oocyte is adequate for normal fertilization and embryo development.
Adult↗
Contraceptive and therapeutic effectiveness of two low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsute patients.
OBJECTIVE: To compare the effectiveness of two very low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsutism. PATIENTS: Eighteen hirsute women were randomized into two different regimens of cyproterone acetate and ethinylestradiol in a reverse sequential pattern: group 1 (0.28 mg ethinylestradiol monthly), group 2 (0.32 mg ethinylestradiol monthly). Both groups received 12.5 mg/day cyproterone acetate for the first 10 days of treatment each month. MAIN OUTCOME MEASURES: Hirsutism scores were measured according to the Ferriman and Gallwey scoring system and side-effects and complications were recorded during the 6 months of therapy. Ovulation was monitored by radioimmunoassay of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone levels. The pituitary response was studied using a gonadotropin releasing hormone test. RESULTS: Hirsutism scores decreased significantly in both groups at the end of the 6 months (-30%). All patients were anovulatory, as documented by the reduction of the LH, FSH, estradiol and progesterone levels. Pretreatment basal LH and FSH levels were higher than LH and FSH levels during the treatment. Side-effects were observed only occasionally with some differences between the two therapeutic regiments. CONCLUSION: Both treatments greatly improve hirsutism, reduce clinical problems and side-effects, guarantee both anovulation and contraceptive effectiveness and afford an optimal control of the menstrual cycle.
Adult↗
Use of recombinant leukemia inhibitory factor in embryo implantation.
Explore the source record for details and available documents.
Culture Media↗
Abnormal uterine contractility in nonpregnant women.
Explore the source record for details and available documents.
Abortion, Habitual↗
Vaginal drug delivery: the first uterine pass effect.
Explore the source record for details and available documents.
Administration, Intravaginal↗
Benign ovarian tumors.
The aim of this study was to analyze whether, in a series of benign ovarian tumors, the diagnosis could be reliably established and whether the surgical treatment was appropriate. All patients underwent the preoperative evaluation and laparotomy was performed in all cases. The patients were followed for up to 3-8 years after surgery. Demolition surgery (mono or bilateral adnexiectomy with hysterectomy) was more frequently performed in postmenopausal women, while conservative surgery (enucleation, monolateral adnexiectomy) was done in fertile women. Evaluation of the treatment in our series shows that the surgical approach was more aggressive than necessary with respect to the histological diagnosis. Although in the serous and mucinous form tumors on can not rule out the possibility of malignancy in the remaining part of the ovary, the current approach should be more conservative, with enucleation of the mass and preservation of the ovary.
Age Distribution↗
Birth of a healthy female after intracytoplasmic sperm injection of cryopreserved human oocytes.
OBJECTIVE: To describe the first birth achieved after intracytoplasmic sperm injection (ICSI) of cryopreserved human oocytes. DESIGN: Case report. SETTING: University of Bologna Hospital, Department of Obstetrics and Gynecology, Reproductive Endocrinology Unit, IVF and Infertility Center. PATIENT(S): One patient undergoing IVF. INTERVENTION(S): Transvaginal ultrasound-guided oocyte retrieval followed by oocyte freezing. Artificial preparation of the endometrium with E2 and P, oocyte thawing, and ICSI. RESULT(S): Four of 12 cryopreserved oocytes survived; using ICSI, 2 underwent normal fertilization but only 1 cleaved. One good-quality 4-cell embryo was transferred. A single gestation was confirmed by ultrasound at the 7th week. Amniocentesis was performed at the 16th week and demonstrated a normal female karyotype of 46,XX. After a normal pregnancy, a healthy female infant was born at the 38th week of gestation. CONCLUSION(S): The combination of ICSI and oocyte cryopreservation is a new tool in assisted reproductive technology.
Adult↗
An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men.
OBJECTIVE: To test the effectiveness, safety, and reversibility of the combined administration of cyproterone acetate and T undecanoate. DESIGN: Open clinical trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Eight healthy men, aged 25-42 years were selected. INTERVENTION(S): Cyproterone acetate, 12.5 mg, and T undecanoate, 80 mg, were administered orally twice daily for 16 weeks. MAIN OUTCOME MEASURE(S): Semen analyses every 2 weeks; physical examination, chemistries, hematology, prostatic-specific antigen, gonadotropins and T levels, and a questionnaire on sexual and behavioral function every 4 weeks. RESULT(S): In all subjects a profound suppression of spermatogenesis occurred; one subject became azoospermic, five subjects had sperm counts of < or = 3 x 10(6)/mL, and in two subjects sperm counts were 4 and 6 x 10(6)/mL in week 16. Sperm counts returned to baseline in all men after hormone administration was discontinued. No changes in metabolic parameters and total prostatic-specific antigen were detected. Hemoglobin and hematocrit decreased statistically significantly at week 16 of treatment and returned to baseline by week 12 of recovery. There was no change in sexual function or behavior. CONCLUSION(S): The oral administration of T undecanoate plus cyproterone acetate induces a profound suppression of spermatogenesis with no major adverse effects. These data suggest the feasibility of oral contraception in men.
Adult↗
Chronobiologic evolution of luteinizing hormone secretion in adolescence: developmental patterns and speculations on the onset of the polycystic ovary syndrome.
OBJECTIVE: To investigate the long-term evolution of the LH circadian profile in adolescent women with anovulatory cycles and normal or elevated LH levels in the first evaluation. DESIGN: Prospective controlled clinical study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(S): Twelve healthy anovulatory adolescent girls aged 12 to 17 years (5 subjects with high plasma LH level and 7 subjects with normal LH level) and four ovulatory subjects as controls. INTERVENTION(S): Blood samples were drawn every 20 minutes for 24 hours beginning at 10:00 A.M. at early and late gynecologic ages. MAIN OUTCOME MEASURE(S): Luteinizing hormone, FSH, E2, T, androstenedione, ovarian volume. RESULT(S): In the first evaluation, the highest plasma LH levels and greatest pulse amplitude were found early in the morning in the normal-LH group and late in the afternoon in the high-LH group. Controls did not display any significant circadian variation in LH secretion. The second evaluation revealed ovulatory cycles in six of seven subjects (85.7%) in the normal-LH group with the disappearance of the circadian rhythm. Two of five (40%) patients with high LH in the first evaluation became ovulatory with a significant decrease of mean LH levels and the disappearance of the circadian rhythm. Girls of both groups who remained anovulatory still displayed the accentuated circadian profiles that were seen at the first evaluation. CONCLUSION(S): An accentuated 24-hour LH periodicity is typical of puberty but disappears in adulthood. The persistence of these rhythms in persistently anovulatory adolescents may indicate a maturational arrest. In particular, the persistence of the high LH circadian profile with the highest values during the day is very similar to that found in polycystic ovary syndrome.
Adolescent↗
Births after transcervical gamete intrafallopian transfer with a falloposcopic delivery system.
OBJECTIVE: To evaluate the safety and efficiency of a new delivery system to perform transcervical GIFT. DESIGN: Evaluation of pregnancy rate (PR), miscarriage rate, ectopic pregnancy rate, and delivery rate. SETTING: Institute of Obstetrics and Gynecology, Reproductive Endocrinology Unit, Infertility and IVF Center. PATIENT(S): Twenty-five patients with patent tubes documented by laparoscopy plus falloposcopy. INTERVENTION(S): Superovulation was induced with GnRH analogue and FSH. Under laparoscopic control, transcervical cannulation of the tube was done using a linear everting catheter incorporating direct falloposcopic vision of the tubal lumen. Two lengths of everting catheter (3 and 6 cm) were used providing either isthmic-ampullary or midampullary placement of the inoculum. A comparison was done in terms of ease of access and transfer, falloposcopic observations, and PRs between the groups. MAIN OUTCOME MEASURE(S): Efficacy was established by evaluating the PR, miscarriage rate, ectopic pregnancy rate, and delivery rate. RESULT(S): The PR was 28% (with no differences between the lengths of everting catheters). No ectopic pregnancies occurred. The abortion rate was 28.6% and the delivery rate was 20%. Neither tubal perforation nor other complications occurred during the procedure. CONCLUSION(S): Falloposcopic GIFT is safe and efficient and may be a less invasive alternative than laparoscopic transfer.
Abortion, Spontaneous↗
Targeted drug delivery in gynaecology: the first uterine pass effect.
The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.
Administration, Intravaginal↗