Impact of embryo quality and endometrial thickness on implantation in natural cycle IVF.

PURPOSE: The aim of this study is to assess the effect of the endometrial thickness and embryo quality on the implantation potential in natural cycle IVF (NC-IVF). METHODS: A retrospective single-center study was performed on 552 single embryo transfers after NC-IVF. The 'quality' of the embryos was evaluated trough the number and regularity of blastomeres, degree of fragmentation, and nuclear content of cells. Endometrial thickness was measured in millimeters with transvaginal ultrasound on the day of hCG application. RESULTS: Our findings showed a statistically significant difference in successful implantation until a plateau of 10 mm is reached (p = 0.001). Only one pregnancy was achieved where endometrial thickness was less than 7 mm, and this resulted in an early miscarriage. The predictors of favorable implantation were fragmentation (≤ 10%, p < 0.05) and the number of blastomeres (preferably 8-cell, p < 0.01) on day 3. Embryo quality (R = 0.052) and endometrial thickness (R = 0.18) were closely related to pregnancy rate. The overall implantation rate per embryo transfer was 18.8%. CONCLUSIONS: Embryo quality and endometrial thickness have a significant impact on implantation in NC-IVF. Highest implantation potential has an 8-cell embryo with ≤ 10% fragmentation in the third day following oocyte retrieval. Endometrial thickness of at least 7 mm seems to be the optimal edge of successful pregnancy.

The role of luteal support during IVF: a qualitative systematic review.

The aim of this review is to provide qualitative evidence-based synthesis regarding efficacy of luteal-phase support on fertility outcome in women undergoing in vitro fertilization (IVF) with respect to clinical or live birth rates and pregnancy loss rates. Although the need of luteal phase support in IVF/ICSI cycles is well-known, the optimal start, dosage, route and the duration of the luteal phase support is still subject of debate. Data suggest that the optimal period to start with the luteal phase support would be between 24-72 hours after oocyte-retrieval and should continue at least until a positive pregnancy test is achieved. However, the majority of IVF-centers worldwide provide progesterone support up to 8 weeks of pregnancy. Among the well-established routes of luteal support, oral dydrogesterone and subcutaneous progesterone represent new and interesting routes of progesterone administration. The current studies support these routes of progesterone administration use in terms of comparable pregnancy rates and pregnancy loss rates to vaginal and intramuscular progesterone. Furthermore, the acceptance and tolerability among patients seems to be even better. In the frozen-thawed embryo transfer, dydrogesterone and vaginal progesterone are not effective as monotherapy treatments; however, when combined there is no reason to avoid one or the other in this setting.

The effect of maternal exercise during pregnancy on abnormal fetal growth.

AIM: To assess the effect of maternal physical activity during pregnancy on abnormal fetal growth. METHODS: The study group of 166 women in gestational week 6-8 exercised regularly three days per week at submaximal intensity during their entire pregnancy and the control group of 168 women received standard antenatal care. The main outcomes were macrosomia and intrauterine growth restriction. RESULTS: The study group had a lower frequency of macrosomia in newborns (6.0% vs 12.5%, P=0.048) and gestational diabetes (1.8% vs 8.3%, P=0.008) than the control-group, but there was no significant difference in intrauterine growth restriction (7.2% vs 6.5%). There was also no significant differences in other perinatal outcomes. CONCLUSIONS: The beneficial effect of maternal physical activity on fetal growth may be caused the impact of aerobic exercise on glucose tolerance. Fitness trainers and kinesiologists, as well as health care providers, should be educated on the benefits of regular exercise during pregnancy and safe physical exercise for pregnant women.

Oral micronized progesterone combined with vaginal progesterone gel for luteal support.

The aim of the present study was to compare the efficacy and satisfaction rate of combined therapy of oral micronized progesterone capsules and vaginal progesterone gel versus monotherapy with vaginal progesterone gel in luteal support. A case-control study was performed on a total number of 370 women aged <45 years undergoing IVF-ET treatment. The patients received either combination of Crinone 8% vaginal gel, 90 mg daily dose and Utrogestan oral capsules 3 x 100 mg, or Crinone 8% vaginal gel, 90 mg daily. Progesterone supplementation begun on the day of oocyte retrieval and continued until pregnancy was tested and in the case of pregnancy until week 8. The comparable rates of ongoing pregnancies were noted with use of combined-progesterone therapy (39.5%) and progesterone-monotherapy (33.5%). Abortion rate (6.4% vs. 15.6%) was significantly lower with the use of combined therapy. Tolerability and satisfaction of both supplements was almost equal but bleeding occurred more frequently in the progesterone-monotherapy group. In conclusion, the efficacy, satisfaction and tolerability of combined and vaginal progesterone supplements were comparable, but bleeding in early pregnancy and abortion rate presented more frequently with the use of vaginal progesterone.

Neonatal outcome of IVF singletons versus naturally conceived in women aged 35 years and over.

PURPOSE: To compare the delivery and neonatal outcome of IVF singleton pregnancies with those conceived spontaneously in primiparous women ≥ 35 years of age. METHODS: Data were collected by the hospital's obstetrics and pediatric staff at the time of examination, hospitalization, delivery and discharge. A total of 283 women with in vitro fertilization (IVF) singleton deliveries were matched according to ethnicity, age, gravidity, smoking habits, body mass index, weight gain in pregnancy, site and time of delivery with consecutive 283 women conceived spontaneously. The outcome measures were mode of delivery, birth weight, preterm birth and perinatal mortality. RESULTS: Cesarean delivery rate was more common in IVF pregnancies (39.9% vs. 25.1%; p < 0.001). Preterm delivery rate, specifically of spontaneous onset was significantly higher in IVF group (18.7%) than in spontaneous conception group (10.3%; p < 0.008). No difference was found in birth weight records (SGA, VLBW, LBW and LGA) or perinatal mortality rate. However, average gestational birth weight was lower among infants conceived after IVF (3,050 ± 587 g vs. 3,130 ± 524 g; p < 0.05). CONCLUSIONS: Singleton IVF pregnancies in primiparous women ≥ 35 years of age have increased perinatal risk associated with higher rates of cesarean section, preterm births and infants of lower average birth weight. Nevertheless, pregnancy and delivery complications, number of infants with low or very low birth weight, small or large birth weight for appropriate gestation did not differ from those of the spontaneous conceptions.

Influence of seasonal variations on in-vitro fertilization success.

This study was designed to investigate the influence of seasonal variations on the number of retrieved ova, fertilization rate, embryo quality rates and pregnancy rate in IVF cycles. Prospective cohort study was conducted on a total number of 2140 cycles in infertile patients undergoing their first IVF cycle between 2000 and 2007 in IVF policlinic. Chi2-test, Pearson's correlation coefficient and one-way analysis of variance were used for statistical analyses. Overall fertilization rate was 77.96% and pregnancy rate 29.15 +/- 2.72% per cycle. Seasonal prevalence of pregnancy rate was highest during fall 33.8 +/- 4.5% and lowest during summer 23.4 +/- 6.2%, but these differences did not reach statistical significance. The study did not show any statistically significant differences in the number of retrieved oocyte, fertilization, and embryo quality according to season. Therefore seasonal changes should not be taken into account in everyday IVF practice.

Eleven consecutive years of respiratory syncytial virus outbreaks in Croatia.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children. METHODS: Over a period of 11 consecutive years (1994-2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay. RESULTS: RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0-6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group. CONCLUSION: The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).

The biennial cycle of respiratory syncytial virus outbreaks in Croatia.

The paper analyses the epidemic pattern of respiratory syncytial virus (RSV) outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994-2005) 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23-25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

Self-reported confidence, attitudes and skills in practical procedures among medical students: questionnaire study.

The aim of our study was to investigate the influence of gender, loss of academic year(s), confidence and attitudes of students on the clinical experience gained by undergraduate education. The survey was conducted during 2004 and 2005 in a sample of 182 students of the 5th and the 6th year at J.J. Strossmayer University School of Medicine in Osijek. The participants were grouped and matched according to their gender, regular studying, the number of time(s) student has performed certain practical medical procedure and the self-confidence arisen by performing one. Furthermore, participants were grouped and compared due to their own assessment of their own practical and theoretical medical knowledge, courses which provide them the least and oppositely--the most practical medical knowledge and their attitude toward current medical faculty curriculum on clinical courses as well as the possibilities of improving them. Fisher's exact test and chi2-test were used to estimate statistical differences between the groups and the parameters in research, while coefficient of contingency was introduced with the aim of defining their correlation. The results showed statistically significant differences between male students who performed more practical medical procedures than female (p < 0.001), non-repeaters performed medical procedures more often than repeaters (p < 0.001, C = 0.658) while repeaters thought higher of their theoretical knowledge than non-repeaters (p < 0.005). Data analysis showed statistically significant correlation between clinical experience and the level of confidence (C = 0.944). This study confirmed influence of male gender, regular studying, better opinion about one's own practical skills and higher confidence in one's own work on greater number of clinical skills performed during undergraduate education.

Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: randomized controlled trial.

OBJECTIVES: To compare efficacy, satisfaction and tolerability of oral dydrogesterone and micronized vaginal progesterone gel used for luteal supplementation. STUDY DESIGN: Randomized controlled trial. A total of 853 infertile women undergoing IVF/ICSI treatment in University Hospital Center "Sisters of Mercy", Zagreb, Croatia. Luteal support was provided as Crinone 8%(®) vaginal progesterone gel (90mg) administered daily, or oral dydrogesterone Duphaston(®) (2× 10mg) administered two times daily. Progesterone was administered from the day of oocyte retrieval (day 0) till pregnancy test or in a case of pregnancy, until week 10. RESULTS: The on-going pregnancy rates were comparable between Crinone 8%(®) vaginal progesterone gel and oral dydrogesterone - Duphaston(®) (28.1% versus 30.3%; OR 1.11 (0.82-1.49 with 95% CI)). Overall satisfaction and tolerability were significantly higher in the dydrogesterone group than in the Crinone group. Vaginal bleeding, interference with coitus and local adverse side effects such as vaginal irritation and discharge occurred significantly more in Crinone group than in dydrogesterone group. CONCLUSIONS: Oral dydrogesterone is effective drug, well tolerated and accepted among patients and can be considered for routine luteal support. CLINICAL TRIAL REGISTRATION NUMBER: NCT01178931; www.clinicaltrials.gov.

Macroprolactinemia: new insights in hyperprolactinemia.

Hypersecretion of prolactin by lactotroph cells of the anterior pituitary may lead to hyperprolactinemia in physiological, pathological and idiopathic conditions. Most patients with idiopathic hyperprolactinemia may have radiologically undetected microprolactinomas, but some may present other causes of hyperprolactinemia described as macroprolactinemia. This condition corresponds to the predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa), that have been postulated to represent prolactin monomer complexed with anti-prolactin immunoglobulins or autoantibodies. The prevalence of macroprolactinemia in hyperprolactinemic populations between 15-46% has been reported. In the pathophysiology of macroprolactinemia it seems that pituitary prolactin has antigenicity, leading to the production of anti-prolactin autoantibodies, and these antibodies reduce prolactin bioactivity and delay prolactin clearance. Antibody-bound prolactin is big enough to be confined to vascular spaces, and therefore macroprolactinemia develops due to the delayed clearance of prolactin rather than increased production. Although the clinical symptoms are less frequent in macroprolactinemic patients, they could not be differentiated from true hyperprolactinemic patients, on the basis of clinical features alone. Although gel filtration chromatography (GFC) is known to be the gold standard for detecting macroprolactin, the polyethylene glycol precipitation (PEG) method has offered a simple, cheap, and highly suitable alternative. In conclusion, macroprolactinemia can be considered a benign condition with low incidence of clinical symptoms and therefore hormonal and imaging investigations as well as medical or surgical treatment and prolonged follow-up are not necessary.

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.

Heterotopic triplet pregnancy complicated with ovarian hyperstimulation syndrome following in vitro fertilization.

Heterotopic pregnancy is a rare event that occurs in less than 1% of pregnancies following in vitro fertilization and embryo transfer, especially when complicated with ovarian hyperstimulation syndrome. We report a case of a 31-year-old woman in the 6th gestational week of pregnancy achieved after in vitro fertilization, who was complaining of acute lower abdominal pain and distension, breathing difficulties and vaginal spotting. Transvaginal ultrasound examination and laboratory tests confirmed the ovarian hyperstimulation syndrome in the presence of two viable gestational sacs. The patient's condition worsened five days later with sudden onset of sharp abdominal pain, nausea and vomiting, along with impaired laboratory test values. Laparoscopy was attempted, but enlarged ovaries and adhesions prevented further procedure, which was then converted to mini-laparotomy. Operative removal of the right tubal pregnancy resulted in uncomplicated course of the intrauterine twin pregnancy and delivery of two healthy neonates by cesarean section at 37 weeks of gestation. Clinicians need to be aware of this rare complication where ovarian hyperstimulation syndrome coexists with heterotopic pregnancy after in vitro fertilization and embryo transfer procedure. Enlarged ovaries may mask accurate ultrasound diagnosis, but timely surgical intervention can prevent fatal consequences and result in normal course and outcome of intrauterine pregnancy.

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.