Adjusted risk for trisomy 21 after the anomaly scan. How accurate is the Fetal Medicine Foundation algorithm?

PURPOSE: To examine the accuracy of the Fetal Medicine Foundation algorithm used to adjust the risk for trisomy 21 after ultrasound findings detected or not at the time of the anomaly scan. METHODS: This was a retrospective study of all amniocenteses performed in a single centre, in singleton pregnancies, between 1998 and 2008. Maternal demographic characteristics, second-trimester ultrasound findings, indications for amniocentesis and karyotype results were reviewed. The algorithm introduced by the Fetal Medicine Foundation was used to calculate the patient specific risk for trisomy 21 using the age related background risk and anomaly scan findings. Expected trisomy 21 cases based on these risks was compared with the actual karyotype results. RESULTS: Overall, 4,511 cases of singleton pregnancies that underwent second-trimester amniocentesis were reviewed. In 572 cases (12.7%), there were markers of chromosomal abnormality and no previous screening for trisomy 21. The expected number of trisomy 21 cases based on maternal age for this population of 572 cases was 1. The expected number of chromosomal abnormalities after adjusting for ultrasound findings based on the algorithm introduced by the Fetal Medicine Foundation was 6.9 (95% confidence interval 3.4-14.3). After karyotyping, in this population there were 6 cases of trisomy 21, 1 case of Trisomy 18 and 1 case of XXY. CONCLUSIONS: The algorithm that adjusts the age related risk of trisomy 21 according to second-trimester anomaly scan findings is very accurate in predicting the modified risk.

Double GnRH-antagonist dose before HCG administration may prevent OHSS in oocyte-donor cycles: a pilot study.

This pilot study evaluated the possibility of preventing early ovarian hyperstimulation syndrome (OHSS) by increasing the daily dose of gonadotrophin-releasing hormone (GnRH) antagonist administration (to twice a day) in oocyte-donor cycles stimulated with the antagonist protocol. The study included 72 oocyte donors who underwent ovarian stimulation using the GnRH antagonist protocol and might have had their cycle cancelled because of ovarian hyper-response. All women were donors presenting a rapid rise of oestradiol > or = 3000 pg/ml early in the stimulation period with more than 15 follicles of < or = 15 mm in diameter. By decreasing the rFSH dose to 75 IU a day with an additional daily dose of GnRH antagonist (0.25 mg twice a day), the oestradiol concentrations were lowered or reached a plateau before human chorionic gonadotrophin was given. A marked decrease in oestradiol concentrations and ovarian volume was observed on the day of oocyte retrieval and 3 days post retrieval. None of the donors needed coasting, were cancelled or developed OHSS. In over-responding oocyte donors, by increasing the usual GnRH-antagonist dose to twice a day during ovarian stimulation, the oestradiol rise can be blocked while a minimal follicular stimulation may continue without the risk of developing OHSS or affecting the outcome.

GnRH antagonists and endometrial receptivity in oocyte recipients: a prospective randomized trial.

The effect that gonadotrophin-releasing hormone (GnRH) antagonists exert on endometrial receptivity has not yet been elucidated. GnRH antagonists might directly affect oocytes, the embryo and/or the endometrium. The aim of this study was to investigate the direct effect of GnRH antagonists on the endometrium in oocyte donation cycles. In an oocyte donation programme, oocytes from each donor (n = 49), stimulated with gonadotrophins and a GnRH antagonist, were equally shared between two different matched recipients. Recipients were randomly allocated to either receive a GnRH antagonist concomitant to donor during their endometrial priming with oestradiol (group I, n = 49) or to solely continue with their endometrial preparation (group II, n = 49). Pregnancy rate was 55.1% in group I and 59.1% in group II. Implantation rate was 26.1% in group I and 24.4% in group II. Endometrial thickness was also similar between the two groups on the day of human chorionic gonadotrophin injection to the donor. In conclusion, GnRH antagonist administration during the proliferative phase at a dose of 0.25 mg per day does not appear to adversely affect endometrial receptivity in oocyte recipients.

Low-dose human chorionic gonadotropin during the proliferative phase may adversely affect endometrial receptivity in oocyte recipients.

The effect of low-dose human chorionic gonadotropin (hCG) administration in the proliferative phase of oocyte recipients was investigated in a prospective randomized trial. Sibling oocytes from the same donor were shared at random among two different recipients. In group I oocyte recipients received 750 IU of hCG every three days concomitant to endometrial preparation with estradiol until hCG injection to the donor, whereas in group II recipients received no hCG during endometrial priming with estradiol. Endometrial thickness was significantly lower in group I compared with group II, although similar endometrial thickness was detected during the mock cycle. Pregnancy rates were significantly lower in group I than in group II (13.6% vs. 45.4%, p<0.05). Implantation rates were also significantly lower in group I (1.7% vs. 22.4%, p<0.01). The study was discontinued prematurely for ethical reasons when 22 cycles were completed, as pregnancy rates were very low in group I. In conclusion, hCG administration in the proliferative phase might directly affect endometrial proliferation and receptivity.

Cytomegalovirus, Toxoplasma gondii and Rubella Vertical Transmission Rates According to Mid-trimester Amniocentesis: A Retrospective Study.

OBJECTIVE: To examine vertical transmission rates of Cytomegalovirus, Toxoplasma Gondii and Rubella infections according to amniotic fluid PCR analysis. METHODS: A retrospective analysis of mid-trimester amniocenteses performed in in pregnancies with diagnosed maternal infection by Cytomegavirus (CMV), Rubella or Toxoplasma gondii during 1994-2008 was performed. Vertical transmission rates were observed according to the presence of the infectious agent's DNA in the amniotic fluid. A univariate regression model was also performed to investigate possible correlations between transmission and epidemiological parameters. RESULTS: Overall, 7033 amniocenteses were performed during study's period, of which 166 (2.4%) with the indication of maternal infection by CMV, Rubella or Toxoplasma. Mean maternal age was 27.4 ± 2.5 years and the mean gestational age at amniocentesis was 18.7 ± 2.5 weeks. Vertical transmission was observed in 21 cases (12.7%). Transmission rate was 17.3% in cases with infection from CMV, 9.5% from Toxoplasma gondii and 7.8% from Rubella (P = .05). Maternal age was the only parameter being significantly associated with increased risk for vertical transmission (P = .04). CONCLUSIONS: According to our results, overall vertical transmission rate marginally exceeds 10%. CMV infection is characterized by relatively higher transplacental transmission rate, while increased maternal age appears to be associated with a higher risk for vertical transmission.

Amniocentesis-related adverse outcomes in diamniotic twins: is there a difference compared to singleton pregnancies?

OBJECTIVE: To investigate whether diamniotic twin gestations are at increased risk of amniocentesis-related adverse outcomes compared to singleton pregnancies. STUDY DESIGN: This was a retrospective study of mid-trimester amniocenteses performed during the period 1993-2009. Cases were divided in two groups, one including singleton (Group 1) and the other diamniotic twin pregnancies (Group 2). All amniocentesis-related adverse outcomes were reviewed, including aspiration of insufficient amniotic fluid, aspiration of hemorrhagic amniotic fluid, repeated puncture and miscarriage. The incidence of these adverse outcomes was compared between the two groups. RESULTS: In total, 6270 cases were included in the study (Group 1, n=6150 and Group 2, n=120). Advanced maternal age was the main indication for amniocentesis in both singleton and twin pregnancies. There was no difference in the incidence of insufficient sample aspiration (0.2% in singletons vs. 0.0% in twins, P=NS), in the incidence of blood-stained amniotic fluid (3.7% in singletons vs. 4.6% in twins, P=NS), in the rate of need for second attempt (2.1% in singletons vs. 1.7% in twins, P=NS) or in the miscarriage rate (0.24% in singletons vs. 0% in twins). CONCLUSION: In our experience, the incidence of amniocentesis-related adverse outcomes is not increased in diamniotic twins compared to singleton pregnancies.