[Ten years of results of in-vitro fertilisation in the Netherlands 1996-2005]. / Tien jaar resultaten van in-vitrofertilisatie in Nederland, 1996-2005.

OBJECTIVE: To present the numbers and results of Dutch IVF treatment from 1996-2005 and to describe trends and differences between centres. DESIGN: Retrospective data-collection, description and analysis. METHOD: The annual statistics from all Dutch IVF centres covering the years 1996-2005 were collected, described and analysed. RESULTS: During this period 138,217 IVF or intracytoplasmic sperm injection (ICSI) cycles were started and 14,881 transfers of frozen-thawed embryos (cryo transfers) were performed. The number of ICSI treatments, in particular, increased to more than 6000 cycles during this period. These treatments resulted in 30,488 ongoing pregnancies (22.1% per cycle started; 19.1% for IVF and 23.4% for ICSI). The ongoing pregnancy rate per cycle increased from 17.6% in 1996 to 24.4% in 2005. The increase after cryo transfers was remarkable (from 9.4% to 17.6%). It is estimated that during this period, about 1 in 52 newborns in the Netherlands was an IVF or ICSI child (1996: 1 in 77, 2005: 1 in 43). There were differences between the individual centres regarding the ongoing pregnancy rate per cycle (range: 15.0-26.4%), the percentage of ICSI (range 20-58%), the percentage of cryo transfers per cycle (range: 4-22%) and the multiple pregnancy rate (range 5-27% in 2005). CONCLUSIONS: In the Netherlands the pregnancy rate has increased over the last 10 years as has the number of IVF treatments. Cryo transfers have become increasingly important and the multiple pregnancy rate has decreased. Although thanks to the collaboration of all centres, the current registry produces important data and works well, there are a number of limitations e.g. the retrospective nature with no validation, which must be tackled over the coming years.

Termination of early pregnancy by the 3 beta-hydroxysteroid dehydrogenase inhibitor epostane.

Progesterone is essential to sustain pregnancy in the first eight weeks. Its synthesis requires the enzyme 3 beta-hydroxysteroid dehydrogenase (3-HSD). We tested the efficacy of an orally administered 3-HSD inhibitor, epostane, in terminating unwanted early pregnancy. Fifty women in the fifth through eight weeks of pregnancy took epostane (200 mg orally every six hours) for seven days. By day 14, pregnancy had been terminated in 42 of the 50 patients (84 percent). Eight women (16 percent) did not abort and underwent dilation and curettage. Vaginal blood loss occurred on average on the third day of epostane treatment, and abortion on the fifth day. Two patients had incomplete abortions; one required a transfusion because of blood loss. Nausea was frequent (in 86 percent), but 76 percent of the participants concluded that epostane was preferable to dilation and curettage. The mean (+/- SD) pretreatment progesterone level (76 +/- 16 nmol per liter) decreased by day 7 (to 16 +/- 11 nmol per liter) and day 14 (to 10 +/- 9 nmol per liter) in those who aborted; levels of human chorionic gonadotropin also decreased from the mean at base line (73 +/- 72 kIU per liter) to 18 +/- 7 kIU per liter on day 7 and 9 +/- 5 kIU per liter on day 14. In those who did not abort after epostane treatment, progesterone levels decreased only slightly by day 7 (to 52 +/- 21 nmol per liter) and rose again (to 81 +/- 18 nmol per liter) by day 14. Among women who responded to epostane, normal menstrual periods had resumed by day 42 after the beginning of treatment in 72 percent. We conclude that epostane taken orally is an effective and safe method for the noninvasive termination of undesired early pregnancy.

PIP: The efficacy of the 3 beta-hydroxysteroid dehydrogenase inhibitor epostane in terminating early pregnancy was investigated in 50 women who were in the 5th-8th weeks of pregnancy. In previous studies, epostane has been shown to reduce progesterone levels significantly in pregnant and nonpregnant women without disruption of subsequent menstrual cycles or adverse effects on adrenal steroidogenesis or hepatic function. The study subjects received 200 mg of epostane orally every 6 hours for 7 days. In 42 women (84%), the pregnancy was terminated by the 14th day after epostane treatment was initiated. There were more responders among primigravidas (90%) than among multigravidas (76%), although the difference was not statistically significant. On average, vaginal blood loss occurred on the 3rd day of treatment and abortion on the 5th day. The mean pretreatment progesterone level (76 + or - 16 nmol/liter) decreased by day 7 to 16 + or - 11 nmol/liter and by day 14 to 10 + or - 9 nmol/liter in women who aborted, while levels of human chorionic gonadotropin decreased from a baseline mean of 73 + or - kIU/liter to 18 + or - 7 kIU/liter on day 7 and 9 + or - 5 kIU/liter on day 14. In women who did not abort, progesterone levels decreased only slightly 7 days after epostane treatment (to 52 + or - 21 nmol/liter) and rose again to 81 + or - 18 nmol/liter by day 14. 86% of study subjects reported treatment-related nausea; however, in 64%, the nausea was no worse than pretreatment nausea. 76% indicated epostane was preferable to dilation and curettage. Normal menstrual periods were resumed by day 42 after the initiation of treatment in 72% of the women who responded to epostane. Overall, these findings suggest that epostane is an effective alternative method for the termination of unwanted pregnancy in the 1st 8 weeks of gestation and should be given serious consideration as a noninvasive alternative to dilation and curettage.

Antiprogestins.

PIP: Epostane is a steroid which inhibits the synthesis of progesterone by inhibiting the enzyme 3-beta-hydroxysteroid dehydrogenase. Progesterone is produced during early pregnancy by the corpus luteum, but after the 7th week, production of progesterone is taken over by the placenta, which also secretes human chorionic gonadotropin. In a clinical trial 50 patients in early (5-8 weeks) pregnancy were given 800 mg of Epostane for 7 days. 84% aborted, including 90% of primigravidas and 76% of multigravidas. Side effects were mild and included nausea, cramps, and vaginal bleeding. In the 16% of patients who did not respond to Epostane there was an increase in cortisol levels. Since cortisol induces human chorionic gonadotropin synthesis and this increases the activity of 3-beta-hydroxysteroid dehydrogenase, it is evident that the nonresponders required a larger dose of Epostane to suppress progesterone synthesis. Epostane is thus a candidate for a "morning after" method to terminate early pregnancy and induce labor.^ieng

[Medicinal interruption of pregnancy using epostane]. / Medicamenteus afbreken van de zwangerschap met epostane.

PIP: Vacuum curettage is the most efficient way of terminating unwanted pregnancies for amenorrhea periods not exceeding 12 weeks. Although fairly safe, the method can cause complications such as infections, bleeding, perforations and incomplete evacuations, and the long term effects are uncertain. The use of medicinal drugs has several advantages, e.g., damage to the cervix can be eliminated. Epostane, a steroid still in clinical trial phase, inhibits progesterone genesis and synthesis in the corpus luteum and placenta, which may lead to abortion. 50 informed and consenting women, above 18 and pregnant less than 8 weeks, determined echographically, were tested with the drug in order to check for efficiency and possible side effects. A dose of 200 mg was given orally during 7 days. Progesterone levels in serum were determined by radioimmunoassay, on day 0, 7 and 14. the results was evaluated on the 14th day. Of the 50, a group of 8 were still pregnant. The progesterone levels in the luteal phase, and the rate of decrease of progesterone concentrations, although on an average higher in the non-respondent group, showed some individual inconsistencies pointing to other hormonal agents responsible for protecting pregnancy. The results also indicated clear but insignificant responsive differences between primi- and multiparous women (90% vs. 76%), which were only minimally reflected in progesterone concentrations. When progesterone production, after 5-6 weeks of amenorrhea, is shifted from the corpus luteum to the placenta, in the corpo-luteal phase, chances of blocking progesterone synthesis are considered theoretically to be the highest. The number of responses during that time period confirmed this. Of importance for dispensation on an out-patient basis is to establish how much blood loss occurs. The tests showed clinically accepted norms.^ieng

Ultrasonographic measurement of the yolk sac.

Ultrasonographic measurements of the yolk sac were made during first trimester in 100 pregnancies. The results were related to the crown-rump length of the embryos and showed an increase in size from 7 to 11 weeks menstrual age. A possible relation between anomalies in yolk sac development and embryonic development was studied in six patients by means of serial weekly ultrasonographic examinations. In one case with absence of the yolk sac embryonic death occurred at 10 weeks menstrual age; the embryo had spina bifida.