Robert Hudeček

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN Double-blind, randomized administration of two 12-week courses of ulipristal acetate. SETTING Gynecology centers. PATIENT(S) A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. INTERVENTION(S) Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. MAIN OUTCOME MEASURE(S) Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. RESULT(S) In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. CONCLUSION(S) Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. CLINICAL TRIAL REGISTRATION NUMBER NCT01629563 (PEARL IV).

Long-term medical management of uterine fibroids with ulipristal acetate

OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN Double-blind, randomized administration of four 12-week courses of ulipristal acetate. SETTING Gynecology centers. PATIENT(S) Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. INTERVENTION(S) Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. MAIN OUTCOME MEASURE(S) Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. RESULT(S) Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. CONCLUSION(S) The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. CLINICAL TRIAL REGISTRATION NUMBER NCT01629563.

Prevention of ovarian function damage by a GnRH analogue during chemotherapy in Hodgkin lymphoma patients

BACKGROUND Frequent negative consequence of chemotherapy (CHT) is ovarian damage and premature ovarian failure (POF). Aim of this prospective case-control study is evaluation of GnRH analogue (GnRH-a) administration to patients with Hodgkin lymphoma (HL) during CHT and prevention of ovarian damage depending upon CHT regimen. METHODS Study group consists of 72 patients in fertile age (18-35 years) with HL diagnosis treated in 2004-2005 by curative CHT together with GnRH analogue (Triptorelin) administration according to a standardized protocol. Patients were divided into three groups according to the stage of disease and treated by three types of CHT regimens (A,B,C) with increased cytotoxicity. Ovarian function of all patients was assessed by gonadotrophin levels (FSH, LH) analysis from peripheral blood before treatment and also 6 and 12 month after it. The number of women with POF after CHT in study group was compared with control group (n = 45, age 18-35 years) of patients treated in 2002-2003 according to the same protocol but without protective GnRH analogue application. RESULTS In study group with GnRH analogue administration during CHT, there was significantly (P < 0.001) fewer cases with POF 6 and 12 month after the end of CHT (37.5% and 20.8%, respectively) than in control group (73.3% and 71.1%, respectively). Comparative analysis depending on cytotoxicity of CHT regimen used showed significant differences in percentage of patient with acquired POF between study and control group only in less aggressive CHT protocols. CONCLUSIONS Study showed a significant reduction of ovarian failure risk in women with HL treated with less aggressive CHT regimens plus a GnRH analogue.

Survival and infertility treatment in male cancer patients after sperm banking

OBJECTIVE To evaluate the relationship between sperm pathology and cancer diagnosis, determine the mortality rate, and evaluate the outcomes of the use of frozen sperm from the sperm bank. DESIGN Prospective study. SETTING University fertility center. PATIENT(S) A total of 619 male patients were referred for sperm freezing before gonadotoxic therapy from 1995 to 2006. INTERVENTION(S) Semen analysis, data verification in the National Oncologic Register, assisted reproduction technologies, and statistical evaluation. MAIN OUTCOME MEASURE(S) Cancer diagnosis and sperm pathology analysis, survival of patients, and infertility treatment success. RESULT(S) Malignant testicular cancer was diagnosed in 43.6% of patients, and malignant neoplasms of the lymphatic and hematopoietic tissues were found in 31.7% of patients. Azoospermia or severe oligospermia (<or=1 million/mL) was detected in 9.7% and 22.6% of patients, respectively. To date, 32 patients (5.2%) sought infertility treatment. Cryopreserved semen was used in 28 couples (87.5%), and 44 intracytoplasmic sperm injection (ICSI) cycles resulted in 13 pregnancies. In total, 74 deaths (11.9%) were reported, 61 of them (82.4%) within 30 months of the cryopreservation of their sperm. CONCLUSION(S) A significant number of patients survived. Intrauterine insemination and ICSI with cryopreserved sperm resulted in deliveries.

Effect of a Selective Progesterone Receptor Modulator on Induction of Apoptosis in Uterine Fibroids In Vivo

Aim. To determine if hormonal treatment induces apoptosis in uterine fibroids. Methods. Immunohistochemical examination of fibroid tissue, using avidin-biotin complex and cleaved caspase-3 antibody for detecting apoptosis, was performed in premenopausal women who underwent 12-week treatment with oral SPRM (6 patients with 5 mg and 5 patients with 10 mg of ulipristal acetate per day) or gonadoliberin agonist (GnRHa, 17 patients) and subsequent myomectomy or hysterectomy for symptomatic uterine fibroids. Ten patients with no presurgical hormonal treatment were used as controls. Results. Apoptosis was present in a significantly higher proportion of patients treated with ulipristal acetate compared to GnRHa (P = 0.01) and to patients with no hormonal treatment (P = 0.01). In contrast to an AI of 158.9 in SPRM patients, the mean AI was 27.5 and 2.0 in GnRHa and control groups, respectively. No statistical difference in the AI was observed between the two groups of patients treated with ulipristal acetate (5 mg or 10 mg). Conclusion. Treatment with ulipristal acetate induces apoptosis in uterine fibroid cells. This effect of SPRM may contribute to their positive clinical effect on uterine fibroids.

Rationale and design of ASTEROID 2, a randomized, placebo- and active comparator-controlled study to assess the efficacy and safety of vilaprisan in patients with uterine fibroids

BACKGROUND Uterine fibroids (UFs) may be treated with progesterone receptor modulators (PRMs), which have been shown to reduce heavy menstrual bleeding and the size of UFs. To date, one PRM (ulipristal acetate) has received regulatory approval for the treatment of UFs; therapy comprises intermittent treatment courses of up to 3months each, followed by a break to allow two menstruations to occur. We report the design of ASTEROID (Assess Safety and efficacy of vilaprisan in patients with uTERine fibrOIDs) 2, a phase 2 study examining the efficacy and safety of a novel PRM, vilaprisan, in women with UFs. METHODS/DESIGN In this randomized multi-arm study, vilaprisan (2mg daily) will be administered in different regimens: continuous treatment for 12 or 24weeks, or two 12-week treatment periods separated by a break to allow one menstruation to occur. Efficacy and safety will be compared with that of ulipristal acetate (5mg daily) and placebo. Patients randomized to receive placebo for 12weeks will also be given active treatment for 12weeks. The primary measure of efficacy will be amenorrhoea rate; secondary measures include time to normalized menstrual bleeding and percentage change in UF volume. Endometrial changes will be monitored throughout the study. DISCUSSION The placebo- and active comparator-controlled trial ASTEROID 2 is the first study to evaluate systematically the efficacy and safety of different treatment regimens of PRMs in women with UFs. The findings of this study will direct the planning of future clinical trials of vilaprisan.

Pelvic floor dysfunction after vaginal and cesarean delivery among singleton primiparas

To compare the prevalence of pelvic floor dysfunction symptoms, including pelvic organ prolapse (POP), urinary incontinence (UI), and fecal incontinence (FI) among primiparous women after vaginal and cesarean delivery.

P33.10: Prenatal ultrasound symptoms of mucolipidosis II in two consecutive pregnancies

prenatal diagnostics of rare case of fetal mucopolysacharidosis type II according ultrasound symptoms is feaseable

P33.12: Prenatal ultrasound diagnosis of craniosynostosis with volume contrast imaging (VCI-C)

Prenatal diagnostics of fetal craniosynostosis using volume contrast imaging. Advanced ultrasound technique VCI-C making diagnostic more accurate

Embryoprotective Therapy of Infertile Women with Polycystic Ovary Syndrome

Infertility is defined as an inability of a woman to carry a pregnancy to a viable foetus. From the perspective of differential diagnosis, infertility differs from sterility, i.e. an inability of a woman to get pregnant. If a woman miscarries on at least three consecutive occasions, this is termed habitual abortion (or habitual pregnancy loss, HPL). Habitual abortion is a standalone nosological unit rather than an accumulation of circumstantial factors, as is confirmed by the lower incidence of foetal chromosomal aberrations in repeatedly miscarrying women compared to spontaneous abortions and a greater involvement of peristatic factors. A loss of all consecutive pregnancies in the first or second trimester is termed primary recurrent miscarriage. Secondary recurrent miscarriage is a situation when repeated miscarriages are preceded by a pregnancy leading to childbirth or an induced abortion. The term dysfertility is used if a woman miscarries on two consecutive occasions only (Zwinger, 2004).