Transfer of zona-free embryos improves outcome in poor prognosis patients: a prospective randomized controlled study

Assisted zona hatching (AZH) has been used in IVF programmes for several years. Recently one group has reported successful pregnancies after transfer of zona-free blastocysts. The aim of our study was to evaluate outcomes after transfer of zona-free day 3 embryos. Two groups of women undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Group A consisted of 52 women under the age of 40 years undergoing their first ICSI attempt. They were alternately randomized to receive zona-free embryos (27 women) and zona-intact embryos (25 women). The second group (group B) included 71 women with a poor prognosis, as defined by age 40 years or more, and/or at least two previous failed IVF/ICSI attempts. They were randomized in a 3:4 ratio (30 zona-free, 41 zona-intact). Acid Tyrode's solution was used to remove the zona pellucida before embryo transfer on day 3 after oocyte collection. The pregnancy rate in group A was not significantly improved when the zona pellucida was removed. However, in the poor prognosis group B, zona removal resulted in a significantly higher pregnancy rate when compared with controls (23 versus 7.3%). We conclude that complete removal of the zona pellucida can improve pregnancy rates in women with poor IVF/ICSI prognosis.     

ICSI using testicular sperm in male hypogonadotrophic hypogonadism unresponsive to gonadotrophin therapy

BACKGROUND: The aim of this study was to assess the use of testicular sperm for ICSI in azoospermic men with hypogonadotrophic hypogonadism unresponsive to gonadotrophin therapy. METHODS: Fifteen patients with hypogonadotrophic hypogonadism who remained azoospermic after hormonal treatment underwent testicular sperm extraction (TESE) and ICSI. These men were recruited from the Egyptian IVF centre over a period of 4 years. All patients were given 75 IU hMG thrice weekly and 5000 IU hCG once or twice weekly for >/=6 months prior to attempting ICSI/TESE. RESULTS: In 11 out of 15 patients (73%), sperm could be retrieved from testicular tissue and were used for ICSI. Two chemical pregnancies resulted but no clinical pregnancies. Nine patients continued gonadotrophin therapy for another 6 months. Sperm appeared in the ejaculate of three of them. The remaining six patients underwent another ICSI cycle, one using cryopreserved sperm and five underwent a second TESE. One chemical pregnancy and three clinical pregnancies were established. One ongoing, one singleton and one twin pregnancies resulted in the delivery of three healthy babies. In total, of 17 ICSI cycles performed using testicular sperm retrieval, the fertilization rate was 41.7% and the cumulative pregnancy rate was 20%. CONCLUSIONS: The use of testicular sperm for ICSI is a treatment option that can be offered to azoospermic males with hypogonadotrophic hypogonadism either not responding or reluctant to continue hormonal treatment. However, prolonged hormonal treatment may improve TESE/ICSI results.     

Optimizing the embryo transfer technique

The technique of embryo transfer is very crucial and great attention and time should be given to this step. In order to optimize the embryo transfer technique, several precautions should be taken. The first and most important is to avoid the initiation of uterine contractility. This can be achieved by the use of soft catheters, gentle manipulation and by avoiding touching the fundus. Secondly, proper evaluation of the uterine cavity and utero-cervical angulation is very important, and can be achieved by performing dummy embryo transfer and by ultrasound evaluation of the utero-cervical angulation and uterine cavity length. Another important step is the removal of cervical mucus so that it does not stick to the catheter and inadvertently remove the embryo during catheter withdrawal. Finally, one has to be absolutely sure that the embryo transfer catheter has passed the internal cervical os and that the embryos are delivered gently inside the uterine cavity.     

Uterine myomata and outcome of assisted reproduction

The aim of this work was to study the effect of uterine myomata on the implantation rate and outcome in in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Among 406 patients, 51 (12.6%) were found to have uterine corporeal myomata. Twelve patients were excluded from the study as they had large myomata, submucous myomata or intramural myomata encroaching on the cavity. These patients were advised to have myomectomy before being enrolled in the IVF/ICSI programme. The remaining patients (n = 39) were sorted according to the number, site and size of the myomata as assessed by transvaginal sonography. Three patients had more than one myoma. Most of the myomata were subserous (72.7%) and the mean diameter of the myomata was 3.5 +/- 0.9 cm. A control group (n = 367) was chosen with normal uteri and no history of uterine reconstruction surgery. The mean age of myoma patients was 34.7 +/- 3.6 years as compared to 34.0 +/- 4.4 years in the control group. The age, period of infertility, body mass index, duration and number of human menopausal gonadotrophin ampoules needed for stimulation, oestradiol levels, number of oocytes retrieved and the fertilization rate were not significantly different in the myoma patients compared to the control group. Fifteen myoma patients (38.5%) subsequently showed one or more pregnancy sacs on ultrasonography of which three (20%) spontaneously aborted during the first trimester and two (13.3%) had preterm labour, as compared to 123 (33.5%), 19 (15.5%) and nine (7.3%) respectively, among the control group (P = 0.27, 0.33 and 0.21). In conclusion, uterine corporeal myomata, not encroaching on the cavity and <7 cm in mean diameter, do not affect the implantation or miscarriage rates in IVF or ICSI.      

Prognostic value of certain enzymatic and hormonal assays in threatened abortion

The following biochemical indices were evaluated comparatively as predictors of the course of threatened abortion: serum oxytocinase, heat stable alkaline phosphatase, leucine aminopeptidase, urinary pregnanediol, and urinary estriol. 36 cases, grouped into controls and pathological cases, were studied. In normal pregnancy, there was a progressive rise in the levels of the serum oxytocinase, leucine aminopeptidase, urinary estriol, and pregnanediol. Serum heat stable alkaline phosphatase showed an undifferentiated range of results in nonthreatened pregnancies. In the group of threatened abortion cases, results were, therefore, considered abnormal if 2 or more successive determinations showed progressive reduction in enzyme or hormonal levels, and abnormality was also diagnosed if the results were below the normal range (published tabularly, per gestational week). The prognostic value of these biochemical indices was as follows: of 16 cases with normal serum oxytocinase values, 31.2% aborted, whereas of 10 with abnormal values, 70% aborted. Of 16 cases with serum leucine normal values, 37.5% aborted, whereas Of 10 abnormal cases, 60% aborted. Of 18 cases with normal heat stable alkaline phosphatase values, 55.5% aborted, whereas of 8 cases with abnormal values, 25% aborted. Of 17 cases with normal urinary estriol determinations, 45% aborted, whereas of 9 cases with abnormal values, 44.5% aborted. And of 17 cases with normal pregnanediol levels, 41% aborted, whereas of 9 cases with abnormal values, 55.5% aborted. These results show that combined estimation of serum oxytocinase and urinary pregnanediol is a reliable parameter in anticipating pregnancy outcome in cases of threatened abortion.     

Meta-analysis of recombinant versus urinary-derived FSH: an update

BACKGROUND: The study aim was to analyse the results of randomized controlled trials (RCTs) comparing recombinant FSH and urinary-derived FSH gonadotrophins [hMG, urinary purified FSH (FSH-P) and highly purified FSH (FSH-HP)] in an IVF/ICSI programme. METHODS: All published truly RCTs using a long protocol of GnRH agonists for down-regulation, were reviewed. Data of pregnancy rate per started cycle were extracted, and odds ratios (OR) calculated using a fixed effect model. Subgroup analysis was carried out to compare recombinant FSH (rFSH) with each product (hMG alone, FSH-P alone and FSH-HP alone). RESULTS: There was no statistically significant difference in the pregnancy rate per started cycle between rFSH and urinary-derived FSH gonadotrophins (OR 1.07; 95% CI 0.94-1.22). Subgroup analysis showed no statistically significant difference in the pregnancy rate per started cycle between rFSH versus hMG (OR 0.81; 95% CI 0.63-1.05), rFSH versus FSH-P (OR 1.24; 95% CI 0.98-1.58) and rFSH versus FSH-HP (OR 1.14; 95% CI 0.94-1.40). There was no significant heterogeneity of treatment effect across the trials. CONCLUSIONS: There is no evidence of clinical superiority in clinical pregnancy rate for rFSH over different urinary-derived FSH gonadotrophins. Additional factors should be considered when choosing a gonadotrophin regimen, including the cost, patient acceptability, safety and drug availability.     

Pregnancy rate is not improved by delaying embryo transfer from days 2 to 3

OBJECTIVE: To compare the outcome of assisted reproduction in day 2 versus day three embryo transfer. DESIGN: Prospective study. PARTICIPANTS: A total of 927 consecutive embryo transfers for IVF and ICSI cycles including 626 embryo transfers on day 2 and 301 on day 3. INTERVENTION: IVF and ICSI. OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: There is no significant difference in the pregnancy rate between ET on day 2 (50.9%) and ET on day 3 (50.5%). CONCLUSION: Embryo transfer could be done on days 2 or 3 according to the convenience of the patient and the medical team. CONDENSATION: Embryo transfer could be done on days 2 or 3 according to the convenience of the medical team with similar results.