Fertility in men with spinal cord injury.

Young men comprise the overwhelming majority of men with spinal cord injury (SCI), the incidence of which has been growing over the years. Due to advances in physical medicine and rehabilitation, remarkable improvements in survival rates have been reported, leading to life expectancies similar to those of the general population. However, many sexual and reproductive functions may be impaired due to erectile or ejaculatory dysfunction and semen abnormalities, characterised by low-sperm motility or viability in SCI males who have not become parents yet. Nevertheless, fatherhood is still possible through the introduction of specialised medical management, by using various medical, technical and surgical methods for sperm retrieval in combination with assisted reproductive techniques. Erectile dysfunction can be managed by the use of phosphodiesterase-5 inhibitors, intracavernosal injections, vacuum devices and penile prostheses. Semen can be obtained from the vast majority of anejaculatory men by medically assisted ejaculation through the use of penile vibratory stimulation or electroejaculation and via prostate massage or surgical procedures. Despite impaired sperm parameters, reasonable pregnancy rates similar to those in able-bodied subfertile cohorts have been reported. However, future research should focus on the optimisation of semen quality in these men and on improving natural ejaculation.

[Hormone replacement therapy and venous thromboembolism]. / Hormonsko nadomjesno lijecenje I venske tromboembolije.

Venous thromboembolism (VTE) is the most important side effect of using hormone replacement therapy (HRT). Biological and epidemiological studies have shown that oral administration of estrogen is associated with an increased risk of VTE compared to transdermal route of administration. Addition of progestogen to estrogen further increases the risk of VTE. Different pharmacological classes of progestogens differently contribute to the risk of VTE. Observational studies observed that the application of micronized progesterone and didrogesteron are safer regarding the risk of VTE compared to other progestins. These results should be further confirmed in the randomized studies. A personal or family history of VTE, existence of hereditary thrombophilia or/and multiple risk factors for VTE represent a strong contraindication to oral HRT use. In such persons the application of transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HRT.

Follicular progesterone elevations with ovulation induction for IVF.

The purpose of this review is to analyse the sources and effects of follicular progesterone elevations during ovarian stimulation, with the underlying mechanisms and preventive strategies on the in vitro fertilisation pregnancy outcome. In the early follicular phase, a flare-up effect of gonadotrophin releasing hormone (GnRH) agonists and incomplete luteolysis in GnRH antagonist regimens can result in significant elevations of progesterone. In the late follicular phase, progesterone elevations in GnRH analogue cycles are the result of the ovarian stimulation itself, driven by high follicle stimulating hormone dosage, estradiol levels, the number of follicles and oocytes. It seems that progesterone elevations (> or = 1.5 ng/mL or 4.77 nmol/L) have a detrimental effect on the outcome of pregnancy, accelerating the endometrial maturation. The most appropriate choice to avoid the negative effects of follicular progesterone elevations is to cancel fresh embryo transfer and to transfer frozen-thawed embryos in natural cycles. To prevent follicular phase elevations it might be preferable to use milder stimulation protocols, earlier trigger of ovulation in high responders and single-blastocyst transfer on day 5. The optimal GnRH analogue protocols during the entire stimulation period appear to be the long agonist as well as "long" and long GnRH antagonist regimens.

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

Fertility preservation with ovarian stimulation protocols prior to cancer treatment.

An increasing trend towards later childbearing has been reported recently in many developed countries. Although the incidence of reproductive age in women who have delayed pregnancy with cancer is 10%, they may be concerned regarding the preservation of ovarian function due to advanced fertile age and with the impact of cancer treatment on later fertility. Among multiple strategies controlled, ovarian stimulation for embryo or oocyte cryopreservation is currently the most established method for fertility preservation. It is important to choose the appropriate ovulation induction protocol prior to oncologic treatment, because most of these patients have only the chance of a single cycle to conceive. Current treatment protocols offer a minimal time delay until oncologic treatment is commenced. In urgent settings, random-start ovarian stimulation represents a new technique which provides a significant advantage by decreasing the total time of the treatment, because it may be started irrespective of the phase of the cycle without compromising oocyte yield and maturity before cancer treatment. However, in patients with oestrogen-sensitive cancers stimulation, protocols using letrozole are currently preferred over tamoxifen regimens, and therefore, it may be highly advisable to use letrozole with gonadotrophins routinely as a safe, effective and novel protocol of ovulation induction.

Characteristics of different phenotypes of polycystic ovary syndrome based on the Rotterdam criteria in the Croatian population.

The aim of this study was to calculate the relative prevalence of all phenotypes of polycystic ovary syndrome (PCOS) and to compare them for anthropometrical, hormonal and metabolic differences according to the Rotterdam Criteria. A total of 300 women with PCOS aged 26.7 +/- 5.6 years (mean +/- SD) and 100 women aged 28.3 +/- 4.1 years (mean +/- SD) were included in a control group. Anthropometrical, hormonal and metabolic parameters were compared between the groups. The most prevalent phenotype in our population was the most severe, phenotype A (56.7%), followed by phenotype D (26.7%) and phenotype C (14.3%). Phenotype B was present in only 2.3% of patients. The four main phenotypes did not differ in age, BMI and WHR. Women with phenotypes A and C had increased levels of LH and an increased LH/FSH ratio along with elevated androgen levels compared to the other groups. Serum glucose levels did not differ between the groups studied, however, higher levels of insulin, GIR and HOMA-IR were found between phenotype A and the control group. Phenotype C PCOS or ovulatory PCOS have the same characteristics as classic PCOS, however in a more mild form, which represents a transition between the classic form and the control group. Compared to the control group, phenotype D had higher mean levels of serum testosterone (still within normal range) along with elevated LH levels and LH/FSH ratio, similar to classic PCOS. However, compared with women diagnosed with PCOS based on hyperandrogenism, oligo-ovulation and polycystic ovaries, these patients demonstrated milder endocrine and metabolic abnormalities. Therefore, from an endocrine point of view, our study supports the inclusion of a normoandrogenic anovulatory phenotype in PCOS diagnostic criteria.

Preovulatory progesterone rise during ovarian stimulation for IVF.

The aim of this review is to analyze the relationship between the preovulatory progesterone (P) rise and the in vitro fertilization (IVF) pregnancy outcome. It also investigates the sources and effects of P level increase, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. The origin of production of P in the early follicular phase is adrenal which shifts toward the ovaries prior to the ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (≤ 1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the time-frame for implantation and thus decreases pregnancy rates. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle.

Treatment of ectopic pregnancy with methotrexate.

The aim of the present study was to analyze retrospectively the safety and success rates of single- and two-dose methotrexate (MTX) protocols for the treatment of hemodynamically stable cases of ectopic pregnancy at University Department of Gynecology and Obstetrics, Zagreb University Hospital Center, during a five-year period. The study evaluated MTX treatment efficacy in 35 women with ectopic pregnancies in relation to the initial levels of human chorionic gonadotropin (hCG) and progesterone. Successful treatment was recorded in 32/35 women, 24/25 on single dose MTX and 8/10 on double dose MTX, whereas 3/35 patients underwent laparoscopy. The mean initial hCG level in all 35 patients on day 0 was 657.54 +/- 592.4 IU/L; 572.99 +/- 488.10 IU/L in those successfully treated with MTX and 1560.30 +/- 890.70 IU/L in those requiring additional laparoscopy (p < 0.005). The mean initial hCG level was 393.10 +/- 305.9 IU/L in patients successfully treated with a single dose of MTX and 973.5 +/- 722.40 IU/L in those with an additional dose of MTX (p < 0.002). The mean initial progesterone level was 16.36 +/-10.70 nmol/L in 35 MTX-treated ectopic pregnancy patients, 13.64 +/- 8.89 nmol/L in those with treatment success and 28.45 +/- 11.32 nmol/L in cases of treatment failure (p < 0.05). The mean level of progesterone on day 0 was 12.74 +/- 830 nmol/L in patients successfully treated with a single dose of MTX and 26.10 +/- 18.80 nmol/L in patients treated with double-dose MTX (p < 0.006). It is concluded that pretreatment values of hCG and progesterone are inversely related to medicamentous treatment success in selected cases ofhemodynamically stable patients, thus they may be used as an important predictor in the management of ectopic pregnancy treated with MTX.

[Treatment of osteoporosis]. / Lijecenje osteoporoze.

Osteoporosis is among the most frequent metabolic diseases affecting 8% to 10% of the population. Since the most disturbing outcome of osteoporosis is a fracture, it is important to identify patients at risk and intervene with pharmacologic therapies and lifestyle changes. Several drugs have shown their ability to reduce vertebral and/or peripheral fractures in patients with osteoporosis. Antiresorptive agents are a basis of therapy, but anabolic drugs have recently widened therapeutic options. Antiresorptive medications, estrogens, selective estrogen receptor modulators, bisphosphonates and calcitonins, work by reducing the rates of bone remodeling. Parathyroid hormone stimulates new bone formation, repairing architectural defects and improving bone density. Strontium ranelate reduces the risk for osteoporotic fractures by both inhibiting bone resorption and increasing bone formation. Other potential therapies for osteoporosis are also reviewed in this article.

Long-term neurodevelopmental outcome of triplets.

OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in triplets and to find out possible connection between the outcome and perinatal events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24-144 months of age correlated with gestational age, birth weight, pregnancy complications, early neonatal period, neonatal cranial ultrasound, period of birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low birth weight and maternal age. In multivariate analysis, both cerebral palsy and minor disabilities correlate significantly with early neonatal complications, neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture of membranes (p=0.047). Children conceived spontaneously do worse than those born after assisted reproduction (p=0.004), those born in the time period 1996-2000 do better than those born before (p=0.021). Seventy-seven percent (77%) of newborns delivered in the time period 1996-2000 and after level 1 antenatal care was introduced, compared with 54% being delivered in the time period before 1996 and with less meticulous types of antenatal care, remain healthy (p=0.015). CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental complications. Stringent perinatal care might appear important determinant of their long-term outcome.

Comparative study of the efficacy and tolerability of two vaginal progesterone formulations, Crinone 8% gel and Utrogestan capsules, used for luteal support.

OBJECTIVE: To compare the efficacy and tolerability of two different types of vaginal progesterone (P), Crinone 8% gel (Fleet Laboratories Ltd., Watford, United Kingdom) and Utrogestan capsules (Laboratories Besins International, Paris, France), used for luteal support after in vitro fertilization (IVF) cycles. DESIGN: Cohort study. SETTING: In Vitro Fertilization Polyclinic, Zagreb, Croatia. PATIENTS: A total of 285 women aged < or =37 years undergoing IVF-embryo transfer treatment. INTERVENTIONS: Patients were treated with either Crinone 8% vaginal P gel (90 mg) administered daily, or Utrogestan vaginal capsules (2 x 100 mg) administered three times daily. Progesterone was administered from the day of oocyte retrieval (day 0) to menses or, in a case of pregnancy, until week 12. MAIN OUTCOME MEASURE: Clinical pregnancy rate. The tolerability and acceptability of both preparations were determined by a questionnaire given to patients. RESULTS: The similar rates of clinical pregnancies (33.1% vs. 30.9%) [corrected] were obtained by using either Crinone 8% vaginal P gel or Utrogestan vaginal capsules. Overall tolerability and acceptability were significantly better in the Crinone group than in the Utrogestan group. CONCLUSIONS: The efficacy of the two vaginal P formulations was nearly the same, but the tolerability and acceptability of Crinone 8% gel were superior, in the opinion of patients.